RU2076108C1 - Derivatives of n-phenylglycine amide, method of their synthesis and pharmaceutical composition showing affinity to receptors of hck and gastrin - Google Patents

Abstract

FIELD: organic chemistry. SUBSTANCE: product: derivatives of N-phenylglycine amide of the general formula (I): R₄-H(CHR₁COR₂)-COCH₂NHCOR₃ where: R₄-H(CHR₁COR₂)-COCH₂NHCOR₃ - hydrogen, (lower) alkyl; R₁ - (lower) alkoxy or R₂; NR₅R₃ - quinolyl or phenylamino-group where phenyl is substituted with one or some substituents taken from halogen, lower alkyl, (lower) alkylthio-group, carboxyl, monooxy(lower)alkyl, (lower)alkoxycarbonyl, oxyimino(lower)alkyl, tetrazolyl-5-(lower)alkyl, (lower)alkyl-COOX, -O-(lower)alkyl-COOX, -CH=CHCOOH, (lower)alkyl-R₃; X - hydrogen, lower alkyl; SO₃H - phenyl substituted with halide, (lower)alkyl, (lower)alkoxy, hydroxyl; polyfluoro(lower)alkyl or (lower)alkoxy, R₄, (lower)alkylthio, (lower)alkoxycarbonyl, carboxyl, acylamino, methylenedioxy, trifluoromethylthio, phenoxy, phenyl, di-(lower)-alkylamino or CON-NO₂ where: R_aR_в - lower alkyl, R_a - phenyl, or R_в and R_a together with nitrogen to which they were bound form: 1,2,3,4-tetrahydroquinolyl-1-, 3.3-di-(lower)-alkylpiperidine, 3,4-dihydro-2H-benzoxazine or morpholine cycle; R_в - (lower)alkyl; R₅ - phenyl possibly substituted with halide; or R₆ and R₅ together with nitrogen atom to which they were bound form: 3,3-di-(lower)-alkylpiperidine cycle, 3,4-dihydro-2H-benzothiazine-1.4-cycle, 1,2,3,4-tetrahydroquinolyl-1-cycle. Reagent 2: isocyanate: OCN-R₆. Reagent 3: amino-derivative: R₉ - R₄-CO-N[CH(R₁)COR₂]. Synthesized product if necessary is hydrolyzed; compound (I) -CH₂-NH₂ is isolated as ester or in the free form. If (I) R₄-H(CHR₁COR₂)-COCH₂NHCOR₃ has R₄-H(CHR₁COR₂)-COCH₂NHCOR₃ - phenylamino-radical with substituted phenyl ring then the corresponding ester is hydrolyzed. If (I) R₃ has R₄-H(CHR₁COR₂)-COCH₂NHCOR₃ - phenyl substituted with hydroxy-group then the corresponding compound (I) R₄ where R₄-H(CHR₁COR₂)-COCH₂NHCOR₃ - phenyl substituted with lower alkoxy-group is hydrolyzed. Pharmacological composition showing affinity to receptors R₄ and gastrin contains compound (I) R₄-H(CHR₁COR₂)-COCH₂NHCOR₃ as an active substance at a single dose 10-500 mg. Synthesized compounds were used in biology and medicine. EFFECT: improved method of synthesis. 7 cl, 2 tbl

Description

к способу их получения и к фармкомпозиции на их основе.The invention relates to the synthesis of biologically active compounds, in particular to new derivatives of N-phenylglycinamide of the formula

to a method for their preparation and to a pharmaceutical composition based on them.

In the formula (I):
R _{1 is} hydrogen, lower alkyl;
R ₂ (ness.) Alkoxy or NR ₅ R ₆ ,
where R ₅ (ness.) alkyl, and R ₆ phenyl,
optionally substituted with halogen or R ₅ and R ₆ together with the nitrogen atom to which they are attached form a 3,3-di (lower) alkyl piperidine ring, a 3,4-dihydro-2H-benzothiazine-1,4-ring or 2,3,4-tetrahydroquinolyl-1st ring;
R ₃ quinolyl or phenylamino group,
in which phenyl is substituted by one or more substituents selected from halogen, lower alkyl, lower alkylthio, carboxyl, monoxy (lower) alkyl, lower alkoxycarbonyl, hydroxyimino lower alkyl, tetrazolyl-5- lower .) alkyl, (ness.) -alkyl-COOX, -O-ness. alkyl-COOX, —CH = CH — COOH, lower alk. SO ₃ H,
X is hydrogen, lower alkyl,
R ₄ phenyl substituted with halogen, lower alkyl, lower alkoxy, hydroxyl, poly (lower) alkyl, nitro, lower alkylthio, lower alkoxycarbonyl, carboxyl, acylamino, methylenedioxy, polyfluoro (ness.) alkoxy, trifluoromethylthio, phenoxy, phenyl, benzyl, phenylamino, dialkylamino or a group CONR _a R _b in which
R _a ness. alkyl, R _b phenyl,
or R _a and R _b together with nitrogen,
to which they are attached and form a 1,2,3,4-tetrahydroquinolyl-1-st, 3,3-di (lower) alkylpiperidine, 3,4-dihydro-2H-benzoxazine or morpholine ring.

в которой R₁, R₂ и R₄ имеют те же самые значения, что указаны выше, выделяют целевой продукт, и при необходимости соединение формулы I, в которой R₄ является фенилом, замещенным алкоксигруппой, подвергают гидролизу с получением соединения I, в котором R₄ является фенилом, замещенным гидроксилом, и/или при необходимости подвергают гидролизу соединение I, содержащее сложноэфирную группу, с получением соединения I в виде соответствующей кислоты.The invention also relates to a method for producing N-phenylglycinamide derivatives of the general formula I (the meaning of the radicals is indicated above), which consists in reacting an isocyanate of the formula
OCN-R ₉ , (II)
in which R ₉ represents a phenyl radical (optionally substituted with one or more substituents selected from halogen atoms and alkyl, alkoxy, alkylthio, nitro, acyl, cyano, sulfamyl, benzoyl, alkoxycarbonyl, a1k-O-a1k , 5-tetrazole and 5-tetrazolylalkyl radicals), with an amino derivative of the formula

in which R ₁ , R ₂ and R ₄ have the same meanings as above, the desired product is isolated, and, if necessary, a compound of formula I in which R ₄ is phenyl substituted with alkoxy is hydrolyzed to give compound I, in which R ₄ is phenyl substituted with hydroxyl and / or optionally hydrolyzing the ester group compound I to give compound I as the corresponding acid.

This reaction is usually carried out in an inert solvent such as tetrahydrofuran, dimethylformamide, a chlorine-containing solvent (e.g. chloroform, 1,2-dichloroethane), an aromatic solvent (e.g. benzene, toluene) at a temperature between 10 ^° C and the boiling point of the solvent .

 Isocyanates with the formula (II) can be obtained by applying or adapting the method described by R. Richter et coll. The Chemistry of Cyanate and their thio derivatives. S.Patai, part 2, Wiley New York, or are commercial.

в которой R₁, R₂ и R₄ имеют те же самые значения, что и в формуле (I).Derivatives with formula (III) can be obtained by applying or adapting the method described in the examples or the method described in T.Wieland et coll. Justus Liebigs Ann. Chem. or as a result of the adaptation of the Gabriel method (Gibson et coll. Angew. Chem. Int. Ed. 7, 919 (1968)), which consists in the fact that they act with hydrazine with the formula
H ₂ N-NHR ₁₀ , (IV)
in which R ₁₀ represents a hydrogen atom or methyl radical, on a derivative with the formula:

in which R ₁ , R ₂ and R ₄ have the same meanings as in formula (I).

This reaction is preferably carried out in an inert solvent, such as alcohol (e.g. methanol, ethanol) or a chlorine-containing solvent (e.g. chloroform, dichloromethane), at a temperature between 0 ^° C. and the boiling point of the solvent.

 The compounds of formula (I) can be purified using conventional known methods, for example, by crystallization, chromatography, extraction, etc.

 The compounds of formula (I) have interesting pharmacological properties. These compounds have a high affinity for cholecystokinin (CCK) and gastrin receptors and are therefore useful in the treatment and prevention of disorders associated with CCK and gastrin at the level of the nervous system and gastrointestinal apparatus.

 Thus, these compounds can be used to treat or prevent psychosis, anxiety disorders, Parkinson's disease, delayed dyskinesia, irritable bowel syndrome, acute pancreatitis, ulcers, intestinal obstruction, some tumors of the lower esophagus, colon and intestines, as well as an appetite regulator.

 These compounds also have a potentiating effect on the analgesic activity of narcotic and non-narcotic drugs.

 The affinity of compounds of formula (I) for CCK receptors was determined by a method similar to that from S. Saito et coll. (J. Nenro. Chem. 37, 483-490 (1981)) at the level of the cerebral cortex and at the level of the pancreas.

In these tests, a C1 ₅₀ value for compounds of formula (I) is usually equal to or less than 1000 nM.

 On the other hand, it is known that compounds that recognize central CCK receptors have similar specificity for gastrin receptors in the gastrointestinal tract (Bock et coll. J. Med. Chem. 32.16-23 (1989); Reyfeld et coll. Am. J. Rysiol. 240, 255-266 (1981); Beinfeld et coll. Neuropeptides, 3, 411-427 (1983)).

The compounds of formula (I) are of low toxicity. Their DL ₅₀ value usually exceeds 40 mg / kg subcutaneously in mice.

Of particular interest are compounds of formula (I) for which:
R ₁ represents a hydrogen atom;
R ₂ represents an alkoxy radical or the radical —NR ₅ R ₆ ;
R ₃ represents a phenylamino radical (the phenyl ring of which is substituted by one or more substituents selected from alkyl, monohydroxyalkyl, carboxy and HOOC-a1k radicals);
R ₄ represents a phenyl radical substituted with one or more substituents selected from halogen atoms and alkoxy, hydroxy, alkoxycarbonyl and R ₅ R ₆ N-CO radicals.

Example 1. To a solution containing 1.25 g of 2- / 2-amino-N- (3-chlorophenyl) -acetamido / -tert-butyl acetate in 20 cm ^{3 of} anhydrous tetrahydrofuran is added at a temperature close to 20 ^o C, 0.6 g of 3-methylphenyl isocyanate. The resulting solution was stirred for 4 hours at a temperature close to 20 ^o C, then concentrated to dryness under reduced pressure (2.7 kPA) and at 40 ^o C. The residual liquid oil was purified by chromatography on 150 g of silica (0.063-0.2 mm) located in a column with a diameter of 2 cm (eluent: cyclohexane-ethyl acetate (75:25 by volume)), collecting fractions of 20 cm ³ . Fractions containing only the desired product are combined and concentrated to dryness under reduced pressure (2.7 kPa) and at 40 ^° C. After crystallization in diisopropyl ether, 0.8 g of 2- {N- (3-chlorophenyl-2- [3] - (3-methylphenyl) -ureido] -acetamido} -tert-butyl acetate, melting at 110 ^o C.

2- / 2-amino-N- (3-chlorophenyl) -acetamido / tert-butyl acetate can be prepared as follows: to a solution containing 2.4 g of 2- / N- (3-chlorophenyl) -2-phthalimidoacetamido / tert-butyl acetate in 40 cm ^{3 of} methanol, 0.75 g of hydrazine hydrate are added. The reaction mixture is stirred at reflux for 3 hours, then concentrated to dryness under reduced pressure (2.7 kPa) and at 40 ^° C. The residue is stirred with 100 cm ^{3 of} diethyl ether, then the insoluble product is separated by filtration, and the filtrate is concentrated to dryness. under reduced pressure (2.7 kPa) and at 40 ^° C. 1.3 g of 2- / 2-amino-N- (3-chlorophenyl) -acetamido / tert-butyl acetate are thus obtained in the form of a liquid oil used as such , as it is, for subsequent syntheses.

2- / N- (3-Chlorophenyl) -2-phthalimidoacetamido / tert-butyl acetate can be prepared as follows. To a solution aged in an argon atmosphere containing 4.8 g of 2- / 3-chlorophenyl / amino-tert-butyl in 60 cm ^{3 of} 1,2-dichloroethane, first add 2.8 g of triethylamine, then dropwise at a temperature close to to 20 ^o C, a solution containing 6.2 g of 2-phthalimidoacetyl chloride in 20 cm ^{3 of} 1,2-dichloroethane. The resulting solution was stirred for 3 hours at a temperature close to 20 ^o C, then 50 cm ^{3 of} water was added to it. The aqueous phase is separated by decantation, then reextracted in 2 times 50 cm ^{3 of} 1,2-dichloroethane. The organic phases are combined, washed with 2 times 10 cm ^{3 of} water, dried on magnesium sulfate, filtered and concentrated to dryness under reduced pressure (2.7 kPa) and at 40 ^o C. The resulting liquid oil is purified by chromatography on 200 g of silica (0.063 -0.2 mm) located in a column with a diameter of 2.5 cm (eluent: cyclohexane-ethyl acetate (50:50 by volume)), collecting fractions of 25 cm ³ . Fractions 3 through 7 are combined and concentrated to dryness under reduced pressure (2.7 kPa) and at 40 ^° C. 2.6 g of 2- / N- (3-chlorophenyl) -2-phthalimidoacetamido / tert-butyl acetate are thus obtained. in the form of a liquid oil, used as it is, for subsequent syntheses.

2- / 3-Chlorophenyl / amino-tert-butyl acetate can be prepared as follows: 5.9 g of tert-butyl bromoacetate are added to a solution containing 7.6 g of 3-chloroaniline in 60 cm ^{3 of} acetonitrile. The resulting solution was stirred at reflux for 4 hours. After cooling, the insoluble product was separated by filtration and washed with 30 cm ^{3 of} acetonitrile. The filtrates are combined and concentrated to dryness under reduced pressure (2.7 kPa) and at 40 ^° C. The residual liquid oil is dissolved in 150 cm ^{3 of} dichloromethane and the resulting solution is washed 4 times with 15 cm ^{3 of} water. The organic phase is dried on magnesium sulfate, filtered, then concentrated to dryness under reduced pressure (2.7 kPa) and at 40 ^o C. 8.1 g of 2- / 3-chlorophenyl / -aminobutyl-tert-acetate are thus obtained in the form of a liquid oil, used as it is, for subsequent syntheses.

 2-Phthalimidoacetyl chloride can be prepared according to the method described in W. Grassmann et E. Schulte-Uebbing, Chem. Ber. 83, 244-247 (1950).

PRI me R 2. Carrying out the synthesis according to a method similar to that described in example 1, but based on 2.5 g of 2- / 2-amino-N- (2-fluorophenyl) -acetamido / -tert-butyl acetate and 1.2 g of 3-methylphenyl isocyanate, 1.75 g of 2- {N- / 2-fluorophenyl / -2- / 3- (3-methylphenyl) -ureido / -acetamido} -tret- is obtained after recrystallization in diisopropyl ether butyl acetate, melting at 148 ^o C.

 2- / 2-amino-N- (2-fluorophenyl) -acetamido / tert-butyl acetate can be obtained by the method similar to that described in example 1 to obtain 2- / 2-amino-N- (3-chlorophenyl ) -acetamido / tert-butyl acetate, but starting from 4.9 g of 2- / N- (2-fluorophenyl) -2-phthalimido-acetamido / tert-butyl acetate and 0.77 g of hydrazine hydrate. Thus, 2.7 g of 2- / 2-amino-N- (2-fluorophenyl) -acetamido / -tert-butyl acetate are obtained in the form of a liquid oil, used as such for subsequent syntheses.

2- / N- (2-Fluorophenyl) -2-phthalimidoacetamido / tert-butyl acetate can be prepared as follows. To a solution aged in an argon atmosphere containing 3.3 g of 2- / 2-fluorophenylamino-tert-butyl acetate in 60 cm ^{3 of} 1,2-dichloroethane, 1.3 g of sodium bicarbonate is added, then dropwise at a temperature close to 20 ^o C, a solution containing 3.1 g of 2-phthalimidoacetyl chloride in 10 cm ^{3 of} 1,2-dichloroethane. The resulting solution is stirred for 3 hours at a temperature close to 20 ^o C, then 20 cm ^{3 of} water are added to it. The aqueous phase is separated by decantation, then reextracted 2 times in 100 cm ^{3 of} 1,2-dichloroethane. The organic phases are combined, dried on magnesium sulfate, filtered, then concentrated to dryness at 40 ^o C and under reduced pressure (2.7 kPa). After recrystallization in petroleum ether, 4.9 g of 2- / N- (2-fluorophenyl) -2-phthalimidoacetamido / tert-butyl acetate, melting at 140 ^° C., are thus obtained.

2- [2-Fluorophenyl] -amino-tert-butyl acetate can be obtained by a method similar to that described in example 1 to obtain 2- / 3-chlorophenylamino-tert-butyl acetate, but starting from 2.45 g of 2- fluoroaniline and 1.95 g of tert-butyl bromoacetate. After recrystallization in petroleum ether, 1.1 g of 2- [2-fluorophenyl] -amino-tert-butyl acetate are thus obtained, melting at 70 ^° C.

PRI me R 3. Carrying out the synthesis according to the method similar to that described in example 1, but based on 6.6 g of 2- / 2-amino-N- (4-methoxyphenyl) -acetamido / -tert-butyl acetate and 3 g of 3-methylphenyl isocyanate, 1.7 g of 2- {N- / 4-methoxyphenyl / -2 / 3- (3-methylphenyl) -ureido / -acetamido} -tert-butyl acetate melting at 158 ^o C.

 2- / 2-amino-N- (4-methoxyphenyl) -acetamido / -tert-butyl acetate can be obtained by the method similar to that described in example 1 to obtain 2- / 2-amino-N- (3-chlorophenyl ) -acetamido / tert-butyl acetate, but starting from 11.7 g of 2- / N- (4-methoxyphenyl) -2-phthalimidoacetamido / tert-butyl acetate and 1.75 g of hydrazine hydrate. Thus, 7 g of 2- / 2-amino-N- (4-methoxyphenyl) -acetamido / -tert-butyl acetate are obtained in the form of a liquid oil, used as it is for subsequent syntheses.

 2- / N- (4-Methoxyphenyl) -2-phthalimidoacetamido / tert-butyl acetate can be obtained by a method similar to that described in example 2 to obtain 2- / 2-phthalimido-N- (2-fluorophenyl) - acetamido / tert-butyl acetate, but starting from 6.7 g of 2- / 4-methoxyphenylamino / tert-butyl acetate 2.5 g of sodium bicarbonate and 6.25 g of 2-phthalimidoacetyl chloride. 11.7 g of 2- (2-phthalimido-N- (4-methoxyphenyl) -acetamido / -tert-butyl acetate are thus obtained in the form of a liquid oil, used as it is for subsequent syntheses.

 2- (4-Methoxyphenylamino) -tert-butyl acetate can be obtained by a method similar to that described in example 1 to obtain 2- / 3-chlorophenyl / amino-tert-butyl acetate, but starting from 7.3 g of 4- methoxyaniline and 5.95 g of tert-butyl bromoacetate. 7.2 g of 2- (4-methoxyphenylamino) tert-butyl acetate are thus obtained in the form of a liquid oil, used as it is for subsequent syntheses.

PRI me R 4. Carrying out the synthesis according to the method similar to that described in example 1, but starting from 2 g of 2- / 2-amino-N- (2-trifluoromethoxyphenyl) -acetamido / -tert-butyl acetate and 0 8 g of 3-methylphenyl isocyanate, 1.35 g of 2- {2- / 3- (3-methylphenyl) -ureido / -N- / 2-trifluoromethoxyphenyl / -acetamido} -tert-butyl acetate melting point are obtained after recrystallization in ethyl acetate at 163 ^o C.

2- / 2-amino-N- (2-trifluoromethoxyphenyl) -acetamido / -tert-butyl acetate can be prepared as follows. To a solution containing 4.4 g of 2- (2-phthalimido-N- (2-trifluoromethoxyphenyl) -acetamido / tert-butyl acetate in 50 cm ^{3 of} ethanol, 105 g of hydrazine hydrate was added. The reaction mixture is stirred for 3 hours at a temperature close to 20 ^° C., then concentrated to dryness under reduced pressure (2.7 kPa) and at 40 ^° C. The residue is stirred with 200 cm ^{3 of} diethyl ether and the insoluble product is separated by filtration. The filtrate is concentrated to dryness under reduced pressure (2.7 kPa) and at 40 ^° C. 2.1 g of 2- / 2-amino-N- (2-trifluoromethoxyphenyl) -acetamido / tert-butyl acetate are thus obtained in the form of a liquid oil used as it is for subsequent syntheses.

2- / 2-Phthalimido-N- (2-trifluoromethoxyphenyl) -acetamido / -tert-butyl acetate can be prepared as follows. To a solution, maintained under an argon atmosphere containing 5 g of 2-phthalimido-N- / 2-trifluoromethoxyphenyl / acetamide in 50 cm ³ of anhydrous tetrahydrofuran is added at a temperature close to 10 ^o C, 0,7 g of sodium hydride (50 wt.) and the resulting suspension is stirred for 1 h at a temperature close to 20 ^° C. Then a solution containing 2.75 g of tert-butyl bromoacetate in 10 cm ^{3 of} anhydrous tetrahydrofuran is added, and stirring is continued for 3 hours at a temperature close to 20 ^o C. The reaction mixture is then poured onto the mixture, chilled d to a temperature close to 0 ^o C, which contains 20 cm ^{3 of} water and 200 cm ^{3 of} ethyl acetate. The aqueous phase is separated by decantation and reextracted 2 times with 20 cm ^{3 of} ethyl acetate. The organic phases are combined, washed 3 times with 25 cm ^{3 of} water, dried on magnesium sulfate, filtered, then concentrated to dryness under reduced pressure (2.7 kPa) and at 40 ^o C. Thus, 4.4 g of 2- / 2- are obtained phthalimido-N- (2-trifluoromethoxyphenyl) -acetamido / -tert-butyl acetate in the form of a liquid oil, used as such for subsequent syntheses.

2-Phthalimido-N- / 2 / trifluoromethoxyphenyl / -acetamide can be prepared as follows. 2.2 g of triethylamine are added to a solution containing 3.6 g of 2-trifluoromethoxyaniline in 50 cm ^{3 of} dichloromethane, which is aged in an argon atmosphere, then, while maintaining the temperature at 20 ^° C, a solution containing 4.6 g of 2-phthalimidoacetyl chloride in 25 cm ³ dichloromethane. The resulting solution was stirred for 3 hours at a temperature close to 20 ^o C, then 25 cm ^{3 of} water was added to it. The formed solid product is separated by filtration, washed 3 times with 5 cm ^{3 of} dichloromethane, then 3 times with 10 cm ^{3 of} water and dried in air. The organic phase of the filtrate is separated by decantation, washed with 2 times 10 cm ^{3 of} distilled water, dried on magnesium sulfate, filtered, then concentrated to dryness under reduced pressure (2.7 kPa) and at 40 ^o C. The resulting solid product is combined with the previous one, and the whole aggregate is recrystallized in ethyl acetate. Thus, 5.1 g of 2-phthalimido-N- [2-trifluoromethoxyphenyl] -acetamide is obtained, melting at 192 ^° C.

PRI me R 5. Carrying out the synthesis according to the method similar to that described in example 1, but based on 3.4 g of 2- / 2-amino-N- (3-trifluoromethoxyphenyl) -acetamido / -tert-butyl acetate and 1.4 g of 3-methylphenyl isocyanate, 1.75 g of 2- {2- / 3- (3-methylphenyl) -ureido / -N- / 3-trifluoromethoxyphenyl / -acetamido} -tret- is obtained after recrystallization in diisopropyl ether butyl acetate, melting at 125 ^o C. 2- / 2-amino-N- (3-trifluoromethoxyphenyl) -acetamido / -tert-butyl acetate can be obtained by the method similar to that described in example 4 to obtain 2- / 2- amino-N- (2-trifluoromethoxyphenyl) - acetamido / tert-butyl acetate, but starting from 3 g of 2- / 2-phthalimido-N- (3-trifluoromethoxyphenyl) -acetamido / tert-butyl acetate and 3.2 g of hydrazine hydrate. Thus, 3.5 g of 2- / 2-amino (3-trifluoromethoxyphenyl) -acetamido / -tert-butyl acetate are obtained in the form of a liquid oil, used as such for subsequent syntheses.

 2- / 2-Phthalimido-N- (3-trifluoromethoxyphenyl) -acetamido / -tert-butyl acetate can be obtained by a method similar to that described in example 4, to obtain 2- / 2-amino-N- (2- trifluoromethoxyphenyl) -acetamido / -tert-butyl acetate, but starting from 3 g of 2 - / - phthalimido-N- (3-trifluoromethoxyphenyl) -acetamido / -tert-butyl acetate, and 3.2 g of hydrazine hydrate. Thus, 3.5 g of 2- / 2-amino (3-trifluoromethoxyphenyl) -acetamido / -tert-butyl acetate are obtained in the form of a liquid oil, used as such, for subsequent syntheses.

 2- / 2-Phthalimido-N- (3-trifluoromethoxyphenyl) -acetamido / tert-butyl acetate can be obtained by a method similar to that described in example 4, to obtain 2 - / - phthalimido-N- (2-trifluoromethoxyphenyl ) -acetamido / -tert-butyl acetate, but based on 4.8 g of 2-phthalimido-N- / 3-trifluoromethoxyphenyl / -acetamide, 0.7 g of an oil suspension of sodium hydride (50 wt.) and 2.75 g of bromine tert-butyl acetate. Thus, 5.1 g of 2- / 2-phthalimido-N- (3-trifluoromethoxyphenyl) -acetamido / -tert-butyl acetate are obtained in the form of a liquid oil, used as it is for subsequent syntheses.

2-Phthalimido-N- / 3-trifluoromethoxyphenyl / -acetamide can be obtained by a method similar to that described in example 4 to obtain 2-phthalimido-N- / 2-trifthomethoxyphenyl / -acetamide, but based on 3.6 g 3-trifluoromethoxyaniline, 2.2 g of triethylamine and 4.6 g of 2-phthalimidoacetyl chloride. After recrystallization in ethyl acetate, 4.8 g of 2-phthalimido-N- [3-trifluoromethoxyphenyl] -acetamide are obtained, melting at 170 ^° C.

PRI me R 6. Carrying out the synthesis according to the method similar to that described in example 1, but based on 3.1 g of 2- / 2-amino-N- / 3-methylphenyl / -acetamido / -tert-butyl acetate and 0.52 g of 3-methylphenyl isocyanate, 1.2 g of 2- (2 - / - (3-methylphenyl) -ureido / -N- / 3-methylphenyl / acetamido) tert-butyl acetate are obtained after recrystallization in diisopropyl ether melting at 97 ^o C.

 2- / 2-amino-N- (3-methylphenyl) -acetamido / tert-butyl acetate can be obtained by the method similar to that described in example 4 to obtain 2- / 2-amino-N- (2-trifluoromethoxyphenyl ) -acetamido / -tert-butyl acetate, but starting from 7.5 g of 2- / N- (3-methylphenyl) -2-phthalimidoacetamido / -tert-butyl acetate and 1.84 g of hydrazine hydrate. Thus, 3.5 g of 2- / 2-amino-N- (3-methylphenyl) -acetamido / -tert-butyl acetate are obtained in the form of a liquid oil, used as it is for subsequent syntheses.

2 // N- (3-Methylphenyl) -2-phthalimidoacetamido / tert-butyl acetate can be obtained by a method similar to that described in example 4 to obtain 2- / 2-phthalimido-N- (2-trifluoromethoxyphenyl) - acetamido / tert-butyl acetate, but starting from 12.5 g of N- / 3-methylphenyl / -2-phthalimidoacetamide, 2.45 g of an oil suspension of sodium hydride (50 wt.) and 8.3 g of bromo-tert-butyl acetate. After recrystallization in diisopropyl ether, 7.6 g of 2- / N- (3-methylphenyl) -2-phthalimidoacetamido / tert-butyl acetate, melting at 166 ^° C., are thus obtained.

N- / 3-Methylphenyl / -2-phthalimidoacetamide can be obtained by a method similar to that described in example 4 to obtain 2-phthalimido-N- / 2-trifluoromethoxyphenyl / -acetamide, but based on 5.36 g of 3- methylaniline, 5.1 g of triethylamine and 11.2 g of 2-phthalimidoacetyl chloride. Thus, 12.7 g of N- / 3-methylphenyl / -2-phthalimidoacetamide are obtained, melting at 207 ^° C.

PRI me R 7. Carrying out the synthesis according to the method similar to that described in example 1, but based on 1.6 g of 2- / 2-amino-N- (3-methoxyphenyl) -acetamido / -N-methyl -N-phenylacetamide and 0.67 g of 3-methylphenyl isocyanate, obtained after recrystallization in acetonitrile of 1.2 g of 2- {N- (3-methoxyphenyl) -2- [3-methylphenyl) -ureido] -acetamido} -N- methyl N-phenylacetamide, melting at 179 ^o C.

 2- / 2-amino-N- (3-methoxyphenyl) -acetamido / -N-methyl-N-phenylacetamide can be obtained by a method similar to that described in example 4 to obtain 2- / 2-amino-N- (2-trifluoromethoxyphenyl) -acetamido / tert-butyl acetate, but starting from 2.3 g of 2- / N- (3-methoxyphenyl) -2-phthalimidoacetamido / -N-methyl-N-phenylacetamide and 0.75 g of hydrazine hydrate . Thus, 1.6 g of 2- / 2-amino-N- (3-methoxyphenyl) -acetamido / -N-methyl-N-phenylacetamide is obtained in the form of a liquid oil, used as it is for subsequent syntheses.

 2- / N- (3-Methoxyphenyl) -2-phthalimidoacetamido / -N-methyl-N-phenylacetamide can be obtained by a method similar to that described in example 4 to obtain 2- / 2-phthalimido-N- (2 -trifluoromethoxyphenyl) -acetamido / -tert-butyl acetate, but starting from 9.15 g of N- / 3-methoxyphenyl / -2-phthalimidoacetamide, 1.6 g of an oil suspension of sodium hydride (50 wt.) and 7.4 g of 2- bromo-N-methyl-N-phenylacetamide. Thus, 5.7 g of 2- / N- (3-methoxyphenyl) -2-phthalimidoacetamido / -N-methylphenylacetamide is obtained in the form of a resin, used as it is for subsequent syntheses.

N- / 3-Methoxyphenyl / -2-phthalimidoacetamide can be obtained by a method similar to that described in example 4 to obtain 2-phthalimido-N- / 2-trifluoromethoxyphenyl / -acetamide, but starting from 6.15 g of 3- methoxyaniline, 5.6 g of triethylamine and 11.2 g of 2-phthalimidoacetyl chloride. 12.3 g of 2-phthalimido-N- [3-methoxyphenyl] -acetamide, melting at 186 ^° C., are thus obtained after recrystallization in acetonitrile.

PRI me R 8. Carrying out the synthesis according to the method similar to that described in example 1, but based on 4.9 g of 2- [2-amino-N- (3-trifluoromethylphenyl) -acetamido] -tert-butyl acetate and 2 g of 3-methylphenyl isocyanate, 1.56 g of 2- / 2- (3-methylphenyl) -ureido) -N- (3-trifluoromethylphenyl) -acetamido / tert-butyl acetate melting at 140 is obtained after recrystallization in diisopropyl ether ^o C.

 2- [Amino-N- (3-trifluoromethoxyphenyl) -acetamido] tert-butyl acetate can be obtained by a method similar to that described in example 4 to obtain 2- / 2-amino-N- (2-trifluoromethoxyphenyl) - acetamido / tert-butyl acetate, but starting from 9 g of 2- / 2-phthalimido-N- (3-trifluoromethylphenyl) -acetamido / tert-butyl acetate and 2.9 g of hydrazine hydrate. Thus, 5.2 g of 2- / 2-amino-N- (3-trifluoromethylphenyl) -acetamido / -tert-butyl acetate are obtained in the form of a liquid oil, used as it is for subsequent syntheses.

 2- / 2-Phthalimido-N- (3-trifluoromethylphenyl) -acetamido / -tert-butyl acetate can be obtained by a method similar to that described in example 4 to obtain 2- / 2-phthalimido-N- (2-trifluoromethoxyphenyl ) -acetamido / -tert-butyl acetate, but based on 16.5 g of 2-phthalimido-N- / 3-trifluoromethylphenyl / -acetamide, 2.3 g of an oily suspension of sodium hydrate (50 wt.) and 9.2 g of bromine tert-butyl acetate. Thus, 9.1 g of 2- [2-phthalimido-N- (3-trifluoromethylphenyl) -acetamido / tert-butyl acetate are obtained in the form of a liquid oil, used as it is for subsequent syntheses.

2-Phthalimido-N- / 3-trifluoromethylphenyl / -acetamide can be obtained by a method similar to that described in example 4 to obtain 2-phthalimido-N- / 2-trifluoromethoxyphenyl / -acetamide, but based on 8.1 g 3-trifluoromethylaniline, 5.1 g of triethylamine and 11.2 g of 2-phthalimidoacetyl chloride. Thus, 16.7 g of 2-phthalimido-N- [3-trifluoromethylphenyl] -acetamide is obtained, melting at 235 ^° C.

PRI me R 9. Carrying out the synthesis according to the method similar to that described in example 1, but based on 3.6 g of 2- / 2-amino-N- (2-ethoxycarbonylphenyl) -acetamido / -tert-butyl acetate and 1.42 g of 3-methylphenyl isocyanate, 1.35 g of 2- {N- / 2-ethoxycarbonylphenyl / -2- / 3- (3-methylphenyl) ureido / acetamido} -tret- is obtained after recrystallization in diisopropyl ether butyl acetate, melting at 142 ^o C.

 2- / 2-amino-N- (2-ethoxycarbonylphenyl) -acetamido / tert-butyl acetate can be obtained by a method similar to that described in example 4 to obtain 2- / 2-amino-N- (2-trifluoromethoxyphenyl ) -acetamido / -tert-butyl acetate, but starting from 6.13 g of 2 - / - N- (2-ethoxycarbonylphenyl) -2-phthalimidoacetamido / -tert-butyl acetate and 1.98 g of hydrazine hydrate. Thus, 3.6 g of 2- / 2-amino-N- (2-ethoxycarbonylphenyl) -acetamido / tert-butyl acetate are obtained in the form of a liquid oil, used as it is for subsequent syntheses.

2- / N- (2-Ethoxycarbonylphenyl) -2-phthalimidoacetamido / tert-butyl acetate can be obtained by a method similar to that described in example 4 to obtain 2- / 2-phthalimido-N- (2-trifluoromethoxyphenyl) - acetamido / tert-butyl acetate, but starting from 7.7 g of N- / 2-ethoxycarbonylphenyl / 2-phthalimidoacetamide, 1.26 oil suspension of sodium hydride (50 wt.) and 4.3 g of tert-butyl bromoacetate. After recrystallization in diisopropyl ether, 6.1 g of 2- / N- (2-ethoxycarbonylphenyl) -2-phthalimidoacetamido / tert-butyl acetate, melting at 127 ^° C., are thus obtained.

N- / 2-Ethoxycarbonylphenyl / -2-phthalimidoacetamide can be obtained by a method similar to that described in example 4 to obtain 2-phthalimido-N- / 2-trifluoromethoxyphenyl / -acetamide, but based on 4.12 g of 2- ethyl aminobenzoate, 2.8 g of triethylamine and 5.6 g of 2-phthalimidoacetyl chloride. Thus, 7.7 g of N- / 2-ethoxycarbonylphenyl / -2-phthalimidoacetamide melting at 187 ^° C. are obtained.

PRI me R 10. Carrying out the synthesis according to the method similar to that described in example 1, but based on 4.7 g of 2- / 2-amino-N- (2-acetylaminophenyl) -acetamido / -acetate tert- butyl and 2 g of 3-methylphenyl isocyanate, obtained after recrystallization in ethyl acetate, 3.6 g of 2- {N- / 2-acetylaminophenyl / -2- / 3- (3-methylphenyl) ureido / -acetamido} tert-butyl acetate, melting at 185 ^o C.

 2- / 2-amino-N- (2-acetylaminophenyl) -acetamido / tert-butyl acetate can be obtained by a method similar to that described in example 4 to obtain 2- / 2-amino-N- (2-trifluoromethoxyphenyl ) -acetamido / tert-butyl acetate, but starting from 7.2 g of 2- / N- (2-acetylaminophenyl) -2-phthalimidoacetamido / tert-butyl acetate and 2.4 g of hydrazine hydrate. Thus, 4.8 g of 2- / 2-amino-N- (2-acetylaminophenyl) -acetamido / tert-butyl acetate are obtained in the form of a liquid oil, used as it is for subsequent syntheses.

2- / N- (2-Acetylaminophenyl) -2-phthalimidoacetamido / tert-butyl acetate can be obtained by a method similar to that described in example 4 to obtain 2- / 2-phthalimido-N- (2-trifluoromethoxyphenyl) - acetamido / tert-butyl acetate, but starting from 9.7 g of N- / 2-acetylaminophenyl / -2-phthalimidoacetamide, 1.6 g of an oil suspension of sodium hydride (50 wt.) and 5.85 g of tert-butyl bromoacetate. After recrystallization in ethyl acetate, 8 g of 2- / N- (2-acetylaminophenyl) -2-phthalimidoacetamido / tert-butyl acetate are obtained, melting at 170 ^° C.

N- / 2-Acetylaminophenyl / -2-phthalimidoacetamide can be obtained by a method similar to that described in example 4 to obtain 2-phthalimido-N- / 2-trifluoromethoxyphenyl / -acetamide, but starting from 6 g of 2-acetylaminoaniline, 4.05 g of triethylamine and 9.6 g of 2-phthalimidoacetyl chloride. Thus, 12.5 g of N- / 2-acetylaminophenyl / -2-phthalimidoacetamide are obtained, melting at 270 ^° C.

PRI me R 11. Carrying out the synthesis according to the method similar to that described in example 1, but based on 4.8 g of 2- / 2-amino-N- (2-chlorophenyl) -acetamido / -tert-butyl acetate and 2.35 g of 3-methylphenyl isocyanate, obtained after recrystallization in a mixture of ethyl acetate and methanol (80:20 by volume), 1.4 g of 2- {N- / 2-chlorophenyl / -2- / 3- ( 3-methylphenyl) -ureido / acetamido} -tert-butyl acetate, melting at 148 ^o C.

 2/2-amino-N- (2-chlorophenyl) -acetamido / tert-butyl acetate can be obtained by a method similar to that described in example 1 to obtain 2- / 2-amino-N (3-chlorophenyl) - acetamido / tert-butyl acetate, but starting from 9.12 g of 2- / N- (2-chlorophenyl) -2-phthalimidoacetamido / tert-butyl acetate and 1 g of hydrazine hydrate. Thus, 5.2 g of 2- / 2-amino-N- (2-chlorophenyl) -acetamido / -tert-butyl acetate are obtained in the form of a liquid oil, used as it is for subsequent syntheses.

2- / N- (2-Chlorophenyl) -2-phthalimidoacetamido / tert-butyl acetate can be obtained by a method similar to that described in example 2 to obtain 2- / N- (2-fluorophenyl) -2-phthalimidoacetamido / tert-butyl acetate, but starting from 8 g of 2- / 2-chlorophenyl / amino-tert-butyl acetate, 3.1 g of sodium bicarbonate and 7.4 g of 2-phthalimidoacetyl chloride. After recrystallization in a mixture of ethyl acetate and cyclohexane (70:30 by volume), 10.6 g of 2- / N- (2-chlorophenyl) -2-phthalimidoacetamido / tert-butyl acetate melting at 164 ^° C are obtained.

 2- [2-Chlorophenyl] -amino-tert-butyl acetate can be obtained by a method similar to that described in example 1 to obtain 2- / 3-chlorophenyl / amino-tert-butyl acetate, but starting from 19.1 g 2-chloroaniline and 9.75 tert-butyl bromoacetate. Thus, 9.3 g of 2- [2-chlorophenyl] -amino-tert-butyl acetate are obtained in the form of a liquid oil, used as it is for subsequent syntheses.

PRI me R 12. Carrying out the synthesis according to the method similar to that described in example 1, but based on 2.4 g of 2- / 2-amino-N- (3,4-methylenedioxyphenyl) -acetamido / -tret -butyl acetate and 1 g of 3-methylphenyl isocyanate, 1.65 g of 2- {N- / 3,4-methylenedioxyphenyl / -2- / 3- (3-methylphenyl) ureido / acetamido} is obtained after recrystallization in ethyl acetate -butyl acetate, melting at 142 ^o C.

2/2-amino-N- (3,4-methylenedioxyphenyl) -acetamido / tert-butyl acetate can be prepared as follows: to a solution containing 4.6 g of 2- / N- (3,4-methylenedioxyphenyl) -2 α-phthalimidoacetamido / β-tert-butyl acetate in 70 cm ^{3 of} dichloromethane, 1.45 g of methylhydrazine are added at a temperature close to 0 ^° C. The reaction mixture is stirred for 16 hours at a temperature close to 20 ^° C., then for 2 hours at a reflux temperature of dichloromethane and cooled to a temperature close to 20 ^° C. 50 cm ^{3 of} water are added and the aqueous phase is separated by decantation, which reextracted 2 times 40 cm ^{3 of} dichloromethane. The organic phases are combined, dried on magnesium sulfate, filtered, then concentrated to dryness under reduced pressure (2.7 kPa) and at 40 ^o C. The resulting liquid oil is purified by chromatography on 50 g of silica (0.063-0.2 mm) located in column with a diameter of 2 cm (eluent: ethyl acetate-methanol (90:10 by volume)), collecting fractions of 20 cm ³ . Fractions 11 to 22 are combined and concentrated to dryness under reduced pressure (2.7 kPa) and at 40 ^o C. Thus, 1.85 g of 2- / 2-amino-N- (3,4-methylenedioxyphenyl) -acetamido / tert-butyl acetate in the form of a liquid oil, used as it is, for subsequent syntheses.

2- / N- (3,4-Methylenedioxyphenyl) -2-phthalimidoacetamido / tert-butyl acetate can be obtained by a method similar to that described in example 2 to obtain 2- / N- (2-fluorophenyl) -2- phthalimidoacetamido / tert-butyl acetate, but starting with 5.15 g of 2- / 3,4-methylenedioxyphenyl / amino-tert-butyl acetate, 1.9 g of sodium bicarbonate and 4.6 g of 2-phthalimidoacetyl chloride. Recrystallization in ethyl acetate gives 8 g of 2- / N- (3,4-methylenedioxyphenyl) -2-phthalimidoacetamido / tert-butyl acetate, melting at 166 ^° C.

2- [3,4-Methylenedioxyphenyl] -amino-butyl acetate can be obtained by a method similar to that described in example 1 to obtain 2- / 3-chlorophenyl / -amino-tert-butyl acetate, but starting from 9 g 3, 4-methylenedioxyaniline and 5.9 g of bromo-tert-butyl acetate. After recrystallization in petroleum ether, 5.2 g of 2- / 3,4-methylenedioxyphenyl / amino-tert-butyl acetate are thus obtained, melting at 80 ^° C.

PRI me R 13. To a solution containing 0.7 g of 2- / 2-amino-N- (4-dimethylaminophenyl) -acetamido / -tert-butyl acetate in 15 cm ^{3 of} anhydrous tetrahydrofuran, is added at a temperature close to 20 ^o C, 0.35 g of 3-methylphenyl isocyanate. The resulting solution was stirred for 3 hours at a temperature close to 20 ^° C., then concentrated to dryness under reduced pressure (2.7 kPa) and at 40 ^° C. After recrystallization of the solid residue in ethyl acetate, 0.7 g of 2- {N- / 4-dimethylaminophenyl / -2- / 3- (3-methylphenyl) ureido / -acetamido} tert-butyl acetate, melting at 105 ^o C.

2- / 2-amino-N- (4-dimethylaminophenyl) acetamido / tert-butyl acetate can be prepared by the following method: to a solution containing 1 g of 2- / N- (4-dimethylaminophenyl) -2-phthalimidoacetamido / - tert-butyl acetate in 20 cm ^{3 of} methanol, 0.15 g of hydrazine hydrate is added. The reaction mixture was stirred at reflux for 3 hours, then concentrated to dryness under reduced pressure (2.7 kPa) and at 40 ^° C. The residue was stirred with 75 cm ^{3 of} diethyl ether and the insoluble product was separated by filtration. The filtrate is concentrated to dryness under reduced pressure (2.7 kPa) and at 40 ^° C. 0.7 g of 2- / 2-amino-N- (4-dimethylaminophenyl) -acetamido / tert-butyl acetate is thus obtained in the form of a liquid oil used as it is for subsequent syntheses.

2- / N- (4-Dimethylaminophenyl) -2-phthalimidoacetamido / tert-butyl acetate can be prepared as follows. To a solution aged in an argon atmosphere containing 2.6 g of 2/4-dimethylaminophenyl / -amino-tert-butyl acetate in 20 cm ^{3 of} 1,2-dichloroethane, 1.4 g of triethylamine are added, then dropwise at a temperature close to 20 ^o C, a solution containing 3.1 g of 2-phthalimidoacetyl chloride in 20 cm ^{3 of} 1,2-dichloroethane. The resulting solution was stirred for 3 hours at a temperature close to 20 ^o C, then 25 cm ^{3 of} water was added to it. The aqueous phase is separated by decantation, then re-extracted 2 times with 50 cm ^{3 of} 1,2-dichloroethane. The organic phases are combined, washed 2 times with 10 cm ^{3 of} water, dried on magnesium sulfate, filtered, then concentrated to dryness under reduced pressure (2.7 kPa) and at 40 ^o C. The resulting liquid oil is purified by chromatography on 100 g of silica (0.063 -0.2 mm), located in a column with a diameter of 2 cm (eluent: dichloromethane-methanol (98: 2 volume)), collecting fractions of 15 cm ³ . Fractions containing only the desired product are combined and concentrated to dryness under reduced pressure (2.7 kPa) and at 40 ^° C. Thus 1.1 g of 2- / N- (4-dimethylaminophenyl) -2-phthalimidoacetamido / - tert-butyl acetate, melting at 170 ^o C.

2- / 4-Dimethylaminophenyl / amino-tert-butyl acetate can be prepared as follows. To a suspension containing 6.3 g of 4-dimethylaminoaniline dichlorohydrate in 50 cm ^{3 of} acetonitrile, 6.1 g of triethylamine are added at a temperature close to 10 ^° C. The resulting suspension is stirred at a temperature close to 20 ^° C. for 30 minutes, then 3 g of tert-butyl bromoacetate are added, and the reaction mixture is stirred at reflux for 4 hours. After cooling, the insoluble product is separated by filtration and washed with 15 cm ^{3 of} acetonitrile, the filtrates are combined and concentrated under reduced pressure (2.7 kPa) and at 40 ^o C. The residual liquid oil is dissolved in 100 cm ^{3 of} dichloromethane and the resulting solution is washed 4 times with 10 cm ³ . The organic phase is dried on magnesium sulfate, filtered, then concentrated to dryness under reduced pressure (2.7 kPa) at 40 ^° C. 2.6 g of 2- / 4-dimethylaminophenyl / amino-tert-butyl acetate are thus obtained in the form of a liquid oil used as it is for subsequent syntheses.

PRI me R 14. Carrying out the synthesis according to the method similar to that described in example 11, but based on 5.1 g of 2- / 2-amino-N- (3-methylthiophenyl) -acetamido / -tert-butyl acetate and 2.2 g of 3-methylphenyl isocyanate, obtained after recrystallization in a mixture of diisopropyl ether and ethyl acetate (80:20 by volume), 2.6 g of 2- {2- / 3- (3-methylphenyl (ureido / - N- (3-methylthiophenyl) -acetamido} -tert-butyl acetate, melting at 135 ^o C.

2- / 2-amino-N- (3-methylthiophenyl) -acetamido / -tert-butyl acetate can be obtained by the method similar to that described in example 1 to obtain 2- / 2-amino-N- (3-chlorophenyl ) -acetamido / tert-butyl acetate, but starting from 7.6 g of 2- / N- (3-methylthiophenyl) -2-phthalimidoacetamido / tert-butyl acetate 2.6 g of hydrazine hydrate and carrying out the synthesis at a temperature close to 20 ^o C. Thus, 5.1 g of 2- / 2-amino-N- (3-methylthiophenyl) -acetamido / tert-butyl acetate are obtained in the form of a liquid oil, used as it is for subsequent syntheses.

2- / N- (3-Methylthiophenyl) -2-phthalimidoacetamido / tert-butyl acetate can be obtained by a method similar to that described in example 1 to obtain 2- / N- (3-chlorophenyl) -2-phthalimidoacetamido / tert-butyl acetate, but starting from 6.8 g of 2- / 3-methylthiophenyl / amino-tert-butyl acetate, 3 g of triethylamine and 6 g of 2-phthalimidoacetyl chloride. After crystallization in diisopropyl ether, 7.6 g of 2- / N- (3-methylthiophenyl) -2-phthalimidoacetamido / tert-butyl acetate, melting at 141 ^° C., are thus obtained.

 2- / 3-Methylthiophenyl / -amino-tert-butyl acetate can be obtained by a method similar to that described in example 1 to obtain 2- / 3-chlorophenyl / amino-tert-butyl acetate, but starting from 8.4 g 3-methylthioaniline and 5.9 g of tert-butyl bromoacetate. Thus, 6.8 g of 2- [3-methylthiophenyl] -amino-tert-butyl acetate is obtained in the form of a liquid oil, used as it is for subsequent syntheses.

PRI me R 15. Carrying out the synthesis according to the method similar to that described in example 11, but based on 3.4 g of 2- / 2-amino-N- (2-chlorophenyl) -acetamido / -N-methyl -N-phenylacetamide and 1.4 g of 3-methylphenyl isocyanate, obtained after recrystallization in acetonitrile 2.2 g of 2- {N- / 2-chlorophenyl / -2- / 3- (3-methylphenyl) -ureido / β-acetamido} -N-methyl-N-phenylacetamide, melting at 180 ^o C.

 2- / 2-amino-N- (2-chlorophenyl) -acetamido / -N-methyl-N-phenylacetamide can be obtained by a method similar to that described in example 4 to obtain 2- / 2-amino-N- (2-trifluoromethoxyphenyl) -acetamido / -tert-butyl acetate, but starting from 5.6 g of 2- / N- (2-chlorophenyl) -2-phthalimidoacetamido / -N-methyl-N-phenylacetamide and 1.9 g of hydrazine hydrate . Thus, 3.3 g of 2- / 2-amino-N- (2-chlorophenyl) -acetamido / -N-methyl-N-phenylacetamide are obtained in the form of a liquid oil, used as it is for subsequent syntheses.

2- / N- (2-Chlorophenyl) -2-phthalimidoacetamido / -N-methyl-N-phenylacetamide can be obtained by a method similar to that described in example 4 to obtain 2- / 2-phthalimido-N- (2 -trifluoromethoxyphenyl) -acetamido / -tert-butyl acetate, but starting from 7.4 g of 2-phthalimido-N- / 2-chlorophenyl / -acetamide, 1.3 g of an oil suspension of sodium hydride (50 wt.) and 5.9 g 2-bromo-N-methyl-N-phenylacetamide. After recrystallization in ethyl acetate, 5.7 g of 2- / N- (2-chlorophenyl) -2-phthalimidoacetamido / -N-methyl-N-phenylacetamide melting at 168 ^° C. are thus obtained.

2-Phthalimido-N- / 2-chlorophenyl / -acetamide can be obtained by a method similar to that described in example 4 to obtain 2-phthalimido-N- / 2-trifluoromethoxyphenyl / -acetamide, but based on 3.8 g 2-chloroaniline, 3.3 triethylamine and 7.2 g of 2-phthalimidoacetyl chloride. Thus, 7.5 g of N- / 2-chlorophenyl / -2-phthalimidoacetamide melting at 250 ^° C. are obtained.

 2-Bromo-N-methyl-N-phenylacetamide can be prepared according to the method described in C. A. Bischoff. Chem. Ber. 34, 2125 (1901).

PRI me R 16. Carrying out the synthesis according to the method similar to that described in example 11, but based on 4.2 g of 2- / 2-amino-N- (2-methoxyphenyl) -acetamido / -tert-butyl acetate and 1.9 g of 3-methylphenyl isocyanate, obtained after recrystallization in ethyl acetate, 3 g of 2- {N- / 2-methoxyphenyl / -2- / 3- (3-methylphenyl) ureido / -acetamido} -tert-butyl acetate, melting at 171 ^o C.

2- / 2-amino-N- (2-methoxyphenyl) -acetamido / -tert-butyl acetate can be obtained by the method similar to that described in example 1 to obtain 2- / 2-amino-N- (3-chlorophenyl ) -acetamido / -tert-butyl acetate, but starting from 8.4 g of 2- / N- (2-methoxyphenyl) -2-phthalimidoacetamido / -tert-butyl acetate 3 g of hydrazine and carrying out the synthesis at a temperature close to 20 ^o C. Thus, 4.2 g of 2- [2-amino-N- (2-methoxyphenyl) -acetamido] -tert-butyl acetate are obtained in the form of a liquid oil, used as such for subsequent syntheses.

2- / N- (2-Methoxyphenyl) -2-phthalimidoacetamido / tert-butyl acetate can be obtained by a method similar to that described in example 1 to obtain 2- / N- (3-chlorophenyl) -2-phthalimidoacetamido / tert-butyl acetate, but starting from 6.4 g of 2- / 2-methoxyphenyl / amino-tert-butyl acetate, 2.7 g of triethylamine and 6 g of 2-phthalimidoacetyl chloride. After recrystallization in diisopropyl ether, 8.4 g of 2- / N- (2-methoxyphenyl) -2 / -phthalimidoacetamido / -tert-butyl acetate, melting at 144 ^° C, are thus obtained.

 2- / 2-Methoxyphenyl / amino-tert-butyl acetate can be obtained by a method similar to that described in example 1 to obtain 2- / 3-chlorophenyl / amino-tert-butyl acetate, but starting from 7.4 g 2-methoxyaniline and 5.9 g of tert-butyl bromoacetate. Thus, 6.4 g of 2- (2-methoxyphenyl) amino-tert-butyl acetate is obtained in the form of a liquid oil, used as it is for subsequent syntheses.

PRI me R 17. To withstand in an argon atmosphere a suspension containing 3.7 g of 2- / 3- (3-methylphenyl) -ureido / -acetic acid in 230 cm ^{3 of} 1,2-dichloroethane is added at a temperature close to 20 ^o C, 4.5 g of 2- / 4-nitrophenyl / amino-tert-butyl acetate. The reaction mixture is heated with stirring until reflux of the solvent. Then, 2.12 g of sulfonyl chloride is added dropwise while maintaining the reflux temperature. After the addition is complete, heating is continued at reflux for 10 minutes, then the reaction mixture is cooled to a temperature close to 10 ^° C and poured into a solution containing 15 g of sodium bicarbonate in 300 cm ^{3 of} water. The aqueous phase is separated by decantation and reextracted 2 times with 50 cm ^{3 of} 1,2-dichloroethane. The organic phases are combined, washed 3 times with 20 cm ^{3 of} water, dried on magnesium sulfate, filtered, then concentrated to dryness under reduced pressure (2.7 kPa) and at 40 ^o C. The residue is purified by chromatography on 200 g of silica (0.063-0 , 2 mm) located in a column with a diameter of 3.5 cm (eluent: cyclohexane-ethyl acetate (50:50 by volume)), collecting fractions of 30 cm ³ . Fractions 16 to 25 are combined and concentrated to dryness under reduced pressure (2.7 kPa) and at 40 ^° C. After recrystallization in ethyl acetate, 2.9 g of 2- {2- / 3- (3-methylphenyl) -ureido / - are obtained N- / 4-nitrophenyl / -acetamido} -tert-butyl acetate, melting at 152 ^o C.

2- / 4-Nitrophenyl / -amino-tert-butyl acetate can be prepared as follows. A mixture consisting of 6.9 g of 4-nitroaniline, 19.5 g of tert-butyl bromoacetate and 9.24 g of sodium bicarbonate is heated with stirring in an argon atmosphere at 160 ^o C for 2 hours 30 minutes, then cooled to a temperature close to 20 ^o C, and poured into a mixture consisting of 150 cm ³ water and 150 cm ³ ethyl acetate. The aqueous phase is separated by decantation and re-extracted 3 times with 50 cm ^{3 of} ethyl acetate. The organic phases are combined, washed 3 times with 20 cm ^{3 of} water, dried on magnesium sulfate, filtered, then concentrated to dryness under reduced pressure (2.7 kPa) and at 40 ^o C. After recrystallization in a mixture of ethyl acetate and cyclohexane (50 : 50 by volume), 7.7 g of 2- / 4-nitrophenyl / amino-tert-butyl acetate are obtained, melting at 124 ^° C.

2- / 3- (3-Methylphenyl) -ureido / -acetic acid can be prepared as follows. To a solution containing 7.5 g of glycine and 8.4 g of sodium bicarbonate in 250 cm ^{3 of} water, 13.3 g of 3-methylphenyl isocyanate is added at a temperature close to 20 ^° C. The reaction mixture is stirred for 18 hours at a temperature close to 20 ^° C., then the insoluble product is separated by filtration and washed with 2 times 30 cm ^{3 of} water, then 2 times 30 cm ^{3 of} ethyl acetate. The filtrates are combined, the aqueous phase is separated by decantation and acidified with 5 N. an aqueous solution of hydrochloric acid to a pH close to 1. The resulting solid product is separated by filtration, washed with 2 times 30 cm ^{3 of} water, then 2 times 30 cm ^{3 of} ethyl acetate and dried in air. Thus, 16.3 g of 2- / 3- (3-methylphenyl) -ureido / -acetic acid are obtained, melting at 225 ^° C.

PRI me R 18. Carrying out the synthesis according to the method similar to that described in example 17, but based on 1.04 g of 2- / 3- (3-methylphenyl) -ureido / -acetic acid, 1.4 g 2- [2,3-dichlorophenyl] -amino-tert-butyl acetate and 0.6 g of sulfonyl chloride, obtained after recrystallization in acetonitrile 0.3 g of 2- {N- / 2,3-dichlorophenyl / -2- / 3- ( 3-methylphenyl) -ureido / -acetamido} -tert-butyl acetate, melting at 135 ^o C.

2- (2,3-Dichlorophenyl) -amino-tert-butyl acetate can be obtained as follows: to a solution containing 32.4 g of 2,3-dichloroaniline in 100 cm ^{3 of} acetonitrile is added at a temperature close to 20 ^o C, 16.8 g of sodium bicarbonate, then a solution containing 39 g of tert-butyl bromoacetate in 50 cm ^{3 of} acetonitrile. The reaction mixture is stirred at reflux for 48 hours, then cooled to a temperature close to 20 ^° C. The insoluble product is separated by filtration and washed with 50 cm ^{3 of} acetonitrile. The filtrates are combined and concentrated to dryness under reduced pressure (2.7 kPa) and at 40 ^o C. The residue is purified by chromatography on 300 g of silica (0.063-0.2 mm) in a column with a diameter of 4 cm (eluent: cyclohexane-ethyl acetate (90: 10 by volume)), collecting fractions of 50 cm ³ . Fractions containing only the desired product are combined and concentrated to dryness under reduced pressure (2.7 kPa) and at 40 ^° C. 33 g of 2- / 2,3-dichlorophenyl / amino-tert-butyl acetate are thus obtained in the form of a liquid oil used as it is for subsequent syntheses.

PRI me R 19. Carrying out the synthesis according to the method similar to that described in example 17, but based on 3.12 g of 2- / 3- (3-methylphenyl) -ureido / -acetic acid, 4.3 g 2- [2-bromophenyl] -amino-tert-butyl acetate and 2 g of sulfinyl chloride are obtained after recrystallization in a mixture of diisopropyl ether and acetonitrile (80:20 by volume), 0.6 g of 2- {N- / 2- bromophenyl) -2- / 3- (3-methylphenyl) -ureido / -acetamido} tert-butyl acetate melting at 158 ^o C.

 2- / 2-Bromo-phenyl / -amino-tert-butyl acetate can be obtained by a method similar to that described in example 18 to obtain 2- / 2,3-dichlorophenyl / -amino-tert-butyl acetate, but starting from 34.4 g of 2-bromoaniline, 8.4 g of sodium bicarbonate and 19.5 g of tert-butyl bromoacetate. Thus, 17.4 g of tert-butyl 2- (2-bromophenyl) aminoacetate are thus obtained in the form of a liquid oil, used as it is for subsequent syntheses.

PRI me R 20. Carrying out the synthesis according to the method similar to that described in example 17, but based on 2.08 g of 2- / 3- (3-methylphenyl) -ureido / -acetic acid, 3.07 g 2- (3-trifluoromethylthiophenyl) -amino-tert-butyl acetate and 1.3 g of sulfinyl chloride are obtained after recrystallization in diisopropyl ether of 0.8 g of 2- {2- / 3- (3-methylphenyl) ureido / -N- / 3 -trifluoromethylthiophenyl) -acetamido} -tert-butyl acetate, melting at 112 ^o C.

 2- (3-Trifluoromethylthiophenyl) -amino-tert-butyl acetate can be obtained by a method similar to that described in example 18 to obtain 2- / 2,3-dichlorophenyl / -amino-tert-butyl acetate, but starting from 19, 3 g of 3-trifluoromethylthioanaline, 8.4 g of sodium bicarbonate and 19.5 g of tert-butyl bromoacetate. Thus, 25.5 g of tert-butyl 2- (3-trifluoromethylthiophenyl) -acetate is obtained in the form of a liquid oil, which is used as it is for subsequent syntheses.

PRI me R 21. To a solution containing 5.5 g of 2- / N- (2-methylphenyl) -2-phthalimidoacetamido / tert-butyl acetate in 90 cm ^{3 of} dichloromethane, is added at a temperature close to 0 ^o C 2.13 g of methylhydrazine. The reaction mixture is stirred for 30 hours at a temperature close to 20 ^° C., then for 1 hour at reflux temperature. After that, 100 cm ^{3 of} water are added, stirred and the aqueous phase is separated by decantation, which is re-extracted 2 times with 60 cm ^{3 of} dichloromethane. The organic phases are combined, washed 2 times with 15 cm ^{3 of} water, dried on magnesium sulfate, filtered, then concentrated to dryness under reduced pressure (2.7 kPa) and at 40 ^o C. Thus, 2- / 2-amino-N- (2-methylphenyl) -acetamido / -tert-butyl acetate as a liquid oil, which is dissolved in 40 cm ^{3 of} anhydrous tetrahydrofuran. 1.77 g of 3-methylphenyl isocyanate was added to this solution, then the reaction mixture was stirred for 1 h at a temperature close to 20 ^o C and concentrated to dryness under reduced pressure (2.7 kPa) and at 40 ^o C. After recrystallization in petroleum ether, 1.05 g of 2- {N- / 2-methylphenyl / -2- / 3- (3-methylphenyl) ureido / acetamido} tert-butyl acetate melting at 133 ^° C are obtained.

2 / N- (2-Methylphenyl) -2-phthalimidoacetamido / tert-butyl acetate can be obtained by a method similar to that described in example 1 to obtain 2-N- (3-chlorophenyl) -2-phthalimidoacetamido / acetate tert-butyl but starting from 5.2 g of tert-butyl 2- [2-methylphenyl] aminoacetate, 2.6 g of triethylamine and 5.3 g of 2-phthalimidoacetyl chloride. After recrystallization in ethyl acetate, 5.5 g of 2- / N- (2-methylphenyl) -2-phthalimidoacetamido / tert-butyl acetate, melting at 140 ^° C., are thus obtained.

 2- [2-Methylphenyl] -amino-tert-butyl acetate can be obtained by a method similar to that described in example 18 to obtain 2- / 2,3-dichlorophenyl / amino-tert-butyl acetate, but starting from 6, 4 g of 2-methylaniline, 2.5 g of sodium bicarbonate and 5.85 g of bromo-tert-butyl acetate. Thus, 5.2 g of 2- / 2-methylphenyl / amino-tert-butyl acetate are obtained in the form of a liquid oil, used as it is for subsequent syntheses.

PRI me R 22. Carry out the synthesis according to a method similar to that described in example 17, but based on 1.8 g of 2- / 4-chlorophenyl / -amino-tert-butyl acetate, 1.56 g of 2- / 3- (3-methylphenyl) -ureido / -acetic acid; and 0.89 g of thionyl chloride. The resulting product is purified by chromatography on 60 g of silica (0.04-0.063 mm) in a column with a diameter of 2.5 cm (eluent: cyclohexane-ethyl acetate (80:20 by volume)) using an excess nitrogen pressure of 40 kPa and collecting fractions of 20 cm ³ . Fractions 21 to 25 are combined and concentrated to dryness under reduced pressure (2.7 kPa) and at 40 ^° C. After crystallization in acetonitrile, 0.5 g of 2- (N- / 4-chlorophenyl / -2- / 3- ( 3-methylphenyl) -ureido / -acetamido) tert-butyl acetate, melting at 125 ^o C.

2- [4-Chlorophenyl] -amino-tert-butyl acetate can be prepared as follows: 9.7 g of bromo-tert-butyl acetate are added to a solution containing 12.7 g of 4-chloroaniline in 100 cm ^{3 of} acetonitrile and the mixture is stirred at the temperature of reflux for 3 hours. The insoluble product is separated by filtration, and the filtrate is concentrated to dryness under reduced pressure (2.7 kPa) and at 40 ^° C. The product obtained is purified by chromatography on 150 g of silica (0.065 0.2 mm), located in a column with a diameter of 2 cm (eluent: cyclohexane-ethyl acetate (70: 30 by volume)), robbing fractions of 20 cm ^3. After concentration under reduced pressure (2.7 kPa) and at 40 ^° C., 11.9 g of 2- / 4-chlorophenyl / amino-tert-butyl acetate are obtained in the form of a liquid oil, used as it is for subsequent syntheses.

PRI me R 23. Carry out the synthesis according to a method similar to that described in example 1, but based on 2.3 g of 2- / 2-amino-N- (3-methoxyphenyl) -acetamido / -tert-butyl -acetate and 1.1 g of 3-methylphenyl isocyanate. The product obtained is purified by chromatography on 150 g of silica (0.04-0.063 mm) in a column with a diameter of 3.5 cm (eluent: cyclohexane-ethyl acetate (70:30 by volume)) using an excess nitrogen pressure of 40 kPa and collecting fractions of 20 cm ³ . Fractions 10 to 16 are combined and concentrated to dryness under reduced pressure (2.7 kPa) and at 40 ^° C. After recrystallization in diisopropyl ether, 2.2 g of 2- {N- / 3-methoxyphenyl / -2- / 3- are obtained (3-methylphenyl) -ureido / -acetamido} -tert-butyl acetate, melting at approximately 60 ^o C.

 2- / 2-amino-N- (3-methoxyphenyl) acetamido / tert-butyl acetate can be obtained by a method similar to that described in example 1 to obtain 2- / 2-amino-N- (3-chlorophenyl) -acetamido / -tert-butyl acetate, but starting from 3.4 g) of 2- / N- (3-methoxyphenyl) -2-phthalimidoacetamido / -tert-butyl acetate and 0.8 g of hydrazine hydrate. Thus, 2.0 g of 2- / 2-amino-N- (3-methoxyphenyl) -acetamido / -tert-butyl acetate is obtained in the form of a liquid oil, used as such for subsequent syntheses.

2- / N- (3-Methoxyphenyl) -2-phthalimidoacetamido / tert-butyl acetate can be prepared as follows: to a solution containing 6.3 g of 2- / 2-chloro-N- (3-methoxyphenyl) -acetamido / tert-butyl acetate in 100 cm ^{3 of} dimethylformamide, 7.5 g of phthalimide in a solution of potassium hydroxide are added. The mixture is stirred at a temperature close to 100 ^o C for 5 hours, then poured into 1000 cm ^{3 of} water. The insoluble product is separated by filtration, washed 3 times with 60 cm ^{3 of} water and dried in air. After recrystallization in diisopropyl ether, 6.7 g of 2- / N- (3-methoxyphenyl) -2-phthalimidoacetamido / tert-butyl acetate are obtained, melting at 138 ^° C.

2- / 2-Chloro-N- (3-methoxyphenyl) -acetamido / -tert-butyl acetate can be prepared as follows. To a solution kept at a temperature close to 15 ^° C containing 7.9 g of 2- / 3-methoxyphenyl / amino-tert-butyl acetate and 6.7 g of triethylamine in 50 cm ^{3 of} 1,2-dichloroethane is added 5, 7 g of chloroacetyl chloride. The mixture is stirred for 6 hours at a temperature close to 60 ^o C. After cooling, the mixture is washed 3 times with 100 cm ^{3 of} water. The organic phase is dried on magnesium sulfate and concentrated to dryness under reduced pressure (2.7 kPa) and at 40 ^° C. After recrystallization in diisopropyl ether, 6.3 g of 2- / 2-chloro-N- (3-methoxyphenyl) are thus obtained -acetamido / -tert-butyl acetate, melting at 110 ^o C.

2- / 3-Methoxyphenyl / -amino-tert-butyl acetate can be obtained by a method similar to that described in example 1 to obtain 2- / 3-chlorophenyl / aminoacetate of tert-butyl, but starting from 12.4 g 4 methoxyaniline and 9.75 g of tert-butyl bromoacetate. The resulting product is purified by chromatography on 200 g of silica (0.063-0.200 mm), which is in a column with a diameter of 7.0 cm (eluent: dichloromethane), collecting fractions of 60 cm ³ . Fractions 10 to 20 are combined and concentrated to dryness under reduced pressure (2.7 kPa) and at 40 ^° C. Thus, 9.8 g of tert-butyl 2- (3-methoxyphenyl) -acetate are obtained in the form of a liquid oil used as such , as it is, for subsequent syntheses.

Example 24. To a solution containing 1.2 g of 2- {N- (4-dimethylaminophenyl) -2 - [(1-imidazolyl) carboxamido] acetamido} tert-butyl acetate in 30 cm ^{3 of} toluene 0.83 g of 3-methylthioaniline is added and the mixture is stirred at reflux for 4 hours. After cooling, 30 cm ^{3 of} ethyl acetate are added, then the resulting solution is washed successively: with 30 cm ^{3 of} water, 2 times 30 cm ³ 1 n . a solution of hydrochloric acid, 2 times 30 cm ^{3 of a} saturated aqueous solution of sodium bicarbonate and 30 cm ^{3 of a} saturated aqueous solution of sodium chloride. The organic phase is dried on magnesium sulfate, then concentrated to dryness under reduced pressure (2.7 kPa) and at 40 ^o C. The residue is purified by chromatography on 100 g of silica (0.065-0.200 mm), which is in a column with a diameter of 2.7 cm ( eluent: methylene chloride), collecting fractions of 70 cm ³ . Fractions 24 to 32 are combined and concentrated to dryness under reduced pressure (2.7 kPa) and at 40 ^° C. After recrystallization in acetonitrile, 0.40 g of 2- {N- / 4-dimethylaminophenyl / -2- / 3- ( 3-methylthiophenyl) -ureido / -acetamido} - tert-butyl acetate, melting at 160 ^o C.

2- {N- / 4-Dimethylaminophenyl / -2 - / (1-imidosolyl) -carboxamido / (acetamido} -tert-butyl acetate can be prepared as follows: To a solution containing 0.58 g of N, N'-diimidazolecarbonyl in 20 cm ^{3 of} anhydrous tetrahydrofuran, a solution containing 1.2 g of 2- / 2-amino-N- (4-dimethylaminophenyl) -acetamido / tert-butyl acetate in 15 cm ^{3 of} anhydrous tetrahydrofuran is added.The solution is stirred for 3 hours at a temperature , close to 20 ^o C, then concentrated to dryness under reduced pressure (2.7 kPa) and at 40 ^o C. The residue was dissolved in 30 cm ^{3 of} ethyl acetate and washed solution sequentially: 4 times with 20 cm ^{3 of} water and with 25 cm ^{3 of a} saturated aqueous solution of sodium chloride.The organic phase is dried on magnesium sulfate, then concentrated to dryness under reduced pressure (2.7 kPa) and at 40 ^o C. After recrystallization in ethyl acetate 1.2 g of 2- {N- / 4-dimethylaminophenyl / -2 - / (1-imidazolyl) -carboxamide / -acetamido} -tert-butyl acetate, melting at 110 ^° C, are obtained.

PRI me R 25. To stirred at a temperature close to 25 ^o C, a solution containing 1.1 g of 2- / 2-amino-N- (4-dimethylaminophenyl) -acetamido / -tert-butyl acetate in 35 cm ³ 1,2-dichloroethane, 0.55 g of triethylamine is added, then 0.9 g of 2-indolecarbonyl chloride dissolved in 35 cm ^{3 of} 1,2-dichloroethane. The reaction mixture is stirred for 18 hours at a temperature close to 25 ^° C. Then 250 cm ^{3 of} dichloromethane are added, then 125 cm ^{3 of a} saturated aqueous sodium hydrogen carbonate solution. The organic phase is washed 2 times with 125 cm ^{3 of} water, dried on magnesium sulfate and concentrated to dryness under reduced pressure (2.7 kPa) and at 40 ^o C. After recrystallization in ethyl acetate, 0.35 g of N- [N- (4- dimethylamino-N-tert-butoxycarbonylmethylphenyl) carbamylmethyl] -2-indolecarboxamide, melting at 230 ^o C.

2-Indolecarbonyl chloride can be prepared as follows. To a suspension containing 1.85 g of 2-indolecarboxylic acid in 40 cm ^{3 of} anhydrous diethyl ether, at a temperature close to 5 ^° C., 0.1 cm ^{3 of} dimethylformamide was added, then 1.5 g of oxalyl chloride dissolved in 10 cm ^{3 of} anhydrous diethyl ether. The reaction mixture is stirred at a temperature close to 25 ^° C. for 2 hours. The ether phase is concentrated to dryness under reduced pressure (2.7 kPa) and at 30 ^° C. 1.8 g of 2-indolecarbonyl chloride are thus obtained, melting at 120 ^o C.

Example 26. To a solution containing 1.85 g of 3- {3- [N- (3-methoxyphenyl) -N- (N-methyl-N-phenylcarbamylmethyl) -carbamylmethyl] - ureido} ethylbenzoate in 75 cm ^{3 of a} mixture of water-tetrahydrofuran dioxane (30:40:30 by volume) are added to 5 cm ³ 1 N. an aqueous solution of sodium hydroxide. The mixture is stirred for 16 hours at a temperature close to 25 ^o C, then concentrated to a volume of about 40 cm ³ under reduced pressure (2.7 kPa) and at 10 ^o C. The resulting solution is diluted with 50 cm ³ water, washed 2 times 50 cm ³ ethyl acetate, acidified to pH 3 using 4 N. a solution of hydrochloric acid and is extracted 2 times with 30 cm ^{3 of} ethyl acetate. The organic phases are combined, washed with 30 cm ^{3 of} water, dried on magnesium sulfate and concentrated to dryness under reduced pressure (2.7 kPa) and at 30 ^o C. After recrystallization in a mixture of acetonitrile dimethylformamide (90:10 by volume), 0.9 g 3- {3- [N- (3-methoxyphenyl) -N- (N-methyl-N-phenylcarbamylmethyl) -carbamylmethyl] - ureido} benzoic acid, melting at 222 ^° C.

3- {3- [N- (3-Methoxyphenyl) -N- (N-methyl-N-phenylcarbamylmethyl) -carbamylmethyl] -ureido} ethyl benzoate can be prepared as follows: to a solution containing 2.1 g of 2- (N- (3-methoxyphenyl) -isocyanato-acetamido - / - N-methyl-N-phenylacetamide in 80 cm ^{3 of} anhydrous tetrahydrofuran, 0.94 g of 3-aminoethyl benzoate are added. The mixture is stirred at a temperature close to 25 ^o C for 18 hours, then concentrated to dryness under reduced pressure (2.7 kPa) and at 40 ^o C. The resulting crude product is purified by chromatography on 80 g of silica (0.065-0.20 mm) located in a column with a diameter of 2.5 cm (eluent: methanol-dichloromethane (20:80 by volume)), applying an excess nitrogen pressure of 40 kPa and collecting fractions of 80 cm ³ . Fractions 8 to 11 are combined and concentrated to dryness under reduced pressure (2.7 kPa) and at 40 ^° C. 1.9 g of 3- {3- [N- (3-methoxyphenyl) -N- (N- methyl-N-phenylcarbamylmethyl) carbamylmethyl] - ureido} ethyl benzoate in the form of a substance such as "meringue", used as it is, for subsequent syntheses.

2- / N- (3-Methoxyphenyl) isocyanatoacetamido / -N-methyl-N-phenylacetamide can be prepared as follows. To a solution kept at a temperature close to 5 ^° C, containing 1.55 g of 2- / 3-methoxyphenyl / amino-N-methyl-N-phenylacetamide and 0.5 g of pyridine in 30 cm ^{3 of} anhydrous tetrahydrofuran, add 0 , 87 g of isocyanatoacetyl chloride dissolved in 10 cm ^{3 of} anhydrous tetrahydrofuran, then the mixture is stirred for 3 hours at a temperature close to 25 ^o C. The insoluble product is separated by filtration, and the filtrate is concentrated to dryness under reduced pressure (2.7 kPa) and 30 ^o C. Thus obtained 1.9 g of 2- / N- (3-methoxyphenyl) -isocyanatoacetamido / -N-methyl-N- phenylacetamide in the form of a liquid oil, used as it is, for subsequent syntheses.

2- [3-Methoxyphenyl] -amino-N-methyl-N-phenylacetamide can be prepared as follows. To a solution containing 5.2 g of 2- / N- (3-methoxyphenyl) trifluoroacetamido / -N-methyl-N-phenylacetamide in 80 cm ^{3 of} ethanol is added at a temperature close to 20 ^° C., 14.2 cm ³ 2 n. an aqueous solution of sodium hydroxide. The reaction mixture is stirred at reflux for 5 minutes, then ethanol is removed by evaporation under reduced pressure (2.7 kPa) and at 40 ^° C. 150 cm ^{3 of} ethyl acetate are added to the residue and the aqueous fraction is separated by decantation. The organic phase is washed 5 times with 20 cm ^{3 of} water, dried on magnesium sulfate, filtered, then concentrated to dryness under reduced pressure (2.7 kPa) and at 40 ^o C. The residual liquid oil is purified by chromatography on 100 g of silica (0.063-0 , 2 mm) located in a column with a diameter of 2.5 cm (eluent: dichloroethane), collecting fractions of 20 cm ³ . Fractions containing only the desired product are combined and concentrated to dryness under reduced pressure (2.7 kPa) and at 40 ^° C. Thus, 2.5 g of 2- / 3-methoxyphenyl / amino-N-methyl-N-phenylacetamido are obtained in the form of a liquid oil, used as it is, for subsequent syntheses.

2- / N- (3-Methoxyphenyl) trifluoroacetamido / -N-methyl-N-phenylacetamide can be prepared as follows. To a solution aged in an argon atmosphere containing 5 g of N- / 3-methoxyphenyl / trifluoroacetamide in 80 cm ^{3 of} anhydrous tetrahydrofuran, 1.4 g of an oil suspension of sodium hydride (50 wt.) Are added at a temperature close to 10 ^° C and stirring the resulting suspension for 30 minutes at a temperature close to 20 ^° C. Then a solution containing 7.9 g of 2-bromo-N-methyl-N-phenylacetamide in 50 cm ^{3 of} anhydrous tetrahydrofuran is added and heated under reflux with stirring for 5 hours. Then the reaction mixture is cooled to a temperature, Lizka to 20 ^o C, and poured into a mixture of 100 cm ³ of water and 150 cm ³ of ethyl acetate. The aqueous phase is separated by decantation and reextracted 2 times with 100 cm ^{3 of} ethyl acetate. The organic phases are combined, washed 3 times with 100 cm ^{3 of} water, dried on magnesium sulfate, filtered, then concentrated to dryness under reduced pressure (2.7 kPa) and at a temperature of 40 ^o C. The resulting liquid oil is purified by chromatography on 100 g of silica ( 0.063-0.2 mm) located in a column with a diameter of 3.5 cm (eluent: dichloromethane), collecting fractions of 20 cm ³ . Fractions containing only the desired product are combined and concentrated to dryness under reduced pressure (2.7 kPa) and at 40 ^° C. Thus, 5.2 g of 2- / N- (3-methoxyphenyl) trifluoroacetamido / -N-methyl -N-phenylacetamide in the form of a liquid oil, used as it is, for subsequent syntheses.

N- / 3-Methoxyphenyl / trifluoroacetamide can be prepared as follows. To an anhydrous solution containing 3.1 g of 3-methoxyanaline in 25 cm ^{3 of} pyridine, 5.25 g of trifluoroacetic anhydride is added at a temperature close to -20 ^° C. The reaction mixture is stirred for 30 min at a temperature close to -20 ^o C, then for 1 h at a temperature close to 0 ^o C, and poured into 150 cm ^{3 of} water, cooled to a temperature close to 0 ^o C. Insoluble the liquid oil is extracted with 200 cm ^{3 of} diethyl ether, and the resulting organic phase is washed 2 times with 30 cm ³ 1 N. an aqueous solution of hydrochloric acid, then 2 times 30 cm ^{3 of} water, dried on magnesium sulfate and concentrated under reduced pressure (2.7 kPa) and at 30 ^o C to dryness. Thus, 5.7 g of N- [3-methoxyphenyl] trifluoroacetamide are obtained in the form of a liquid oil, used as it is for subsequent syntheses.

2-Bromo-N-methyl-N-phenylacetamide can be prepared as follows. To a solution containing 10.7 g of N-methylaniline in 65 cm ^{3 of} dichloromethane, 11.1 g of triethylamine and a solution containing 20.4 g of bromoacetyl bromide in 10 cm ^{3 of} dichloromethane are successively added at a temperature close to -5 ^° C. The resulting suspension is stirred for 2 hours at a temperature close to 20 ^° C., then 25 cm ^{3 of} water are added to it. The aqueous phase is separated by decantation and reextracted 2 times with 15 cm ^{3 of} dichloromethane. The organic phases are combined, washed 3 times with 25 cm ^{3 of} water, dried on magnesium sulfate, filtered, then concentrated to dryness under reduced pressure (2.7 kPa) and at 40 ^o C. 100 cm ^{3 of} anhydrous diethyl ether are added to the residual liquid oil: the insoluble product is separated by filtration and washed 3 times with 15 cm ^{3 of} diethyl ether. The filtrates are combined and concentrated to dryness under reduced pressure (2.7 kPa) and at 40 ^° C. Thus, 20.5 g of 2-bromo-N-methyl-N-phenylacetamide are obtained in the form of a liquid oil, used as it is, for subsequent syntheses.

 Isocyanatoacetyl chloride can be prepared according to the method described in Yoshio Iwakura et Coll. J. Org. Chem. 30, 1158 (1965).

PRI me R 27. To a solution containing 4.8 g of 2 - {- 2-amino-N- [2- (3,3-dimethylpiperidino) -carbonylphenyl] acetamido} - tert-butyl acetate in 40 cm ³ anhydrous tetrahydrofuran, is added at a temperature close to 20 ^o C, 1.2 g of 3-methylphenyl isocyanate. The resulting solution was stirred for 4 hours at a temperature close to 20 ^o C, then concentrated to dryness under reduced pressure (2.7 kPa) and at 40 ^o C. The residual liquid oil was purified by chromatography on 150 g of silica (0.063-0.2 mm) located in a column with a diameter of 3.5 cm (eluent: dichloromethane-methanol (98: 2 by volume), collecting fractions of 50 cm ^3. Fractions containing only the desired product are combined and concentrated to dryness under reduced pressure (2, 7 kPa) and at 40 ^o C. After recrystallization in ethyl acetate, 3.2 g of 2 - {- N- [2- (3,3-dimethylpiperidino) are obtained ) -carbonylphenyl] -2- [3- (3-methylphenyl) -ureido] acetamido} tert-butyl acetate, melting at 207 ^o C.

2- {2-amino-N- [2- (3,3-dimethylpiperidino) carbonylphenyl] acetamido} - tert-butyl acetate can be prepared as follows. 1.9 g of hydrazine hydrate are added to a solution containing 6.3 g of 2- {N- [2- (3,3-dimethylpiperidino) -carbonylphenyl] -2-phthalimidoacetamido} tert-butyl acetate in 100 cm ^{3 of} methanol. The reaction mixture is heated at reflux for 4 hours, then concentrated to dryness under reduced pressure (2.7 kPa) and at 40 ^° C. The residual liquid oil is dissolved in 200 cm ^{3 of} ethyl acetate and 50 cm ^{3 of} water are added to the resulting solution. The aqueous phase is separated by decantation, then reextracted 2 times with 30 cm ³ ethyl acetate. The organic phases are combined, washed 2 times with 30 cm ^{3 of} water, dried on magnesium sulfate, filtered, then concentrated to dryness under reduced pressure (2.7 kPa) and at 40 ^o C. Thus, 4.8 g of 2 - {- 2 -amino-N- [2- (3,3-dimethylpiperidino) -carbonylphenyl] -acetamido} -tert-butyl acetate in the form of a liquid oil, used as it is for subsequent syntheses.

2- {N- [2- (3,3-Dimethylpiperidino) -carbonylphenyl] -2-phthalimidoacetamido} - tert-butyl acetate can be prepared as follows. To a solution aged in an argon atmosphere containing 8.4 g of N- / 2- (3,3-dimethylpiperidine) -carbonylphenyl / -2-phthalimidoacetamide in 100 cm ^{3 of} anhydrous tetrahydrofuran is added at a temperature close to 10 ^o C, 1, 05 g of an oil suspension of sodium hydride (50 wt.) And the resulting mixture was stirred for 1 h at a temperature close to 20 ^o C. Then a solution containing 4.5 g of tert-butyl bromoacetate in 25 cm ^{3 of} anhydrous tetrahydrofuran was added, and stirred another 3 hours at a temperature close to 20 ^o C, then 4 hours at the temperature of formation of the reflux of the solvent. Then the reaction mixture is poured to cooled to a temperature close to 0 ^o C, a mixture consisting of 30 cm ³ distilled water and 200 cm ³ ethyl acetate. The aqueous phase is separated by decantation and reextracted 2 times with 20 cm ^{3 of} ethyl acetate. The organic phases are combined, washed 3 times with 25 cm ^{3 of} water, dried on magnesium sulfate, filtered, then concentrated to dryness under reduced pressure (2.7 kPa) and at 40 ^o C. 6.5 g of 2- {N- / 2- (3,3-dimethylpiperidino) -carbonylphenyl / -2-phthalimidoacetamido} tert-butyl acetate as an amorphous solid, which is used as it is for subsequent syntheses.

N- / 2- (3,3-Dimethylpiperidino) -carbonylphenyl / -2-phthalimidoacetamide can be prepared as follows. To a solution maintained in an argon atmosphere containing 7 g of 2- (3,3-dimethylpiperidino) -carbonylaniline in 150 cm ^{3 of} dichloromethane, 3.3 g of triethylamine are added, then, keeping the temperature at 20 ^° C, a solution containing 6.8 g 2-phthalimidoacetyl chloride in 100 cm ^{3 of} dichloromethane. The resulting solution was stirred for 3 hours at a temperature close to 20 ^° C., then 100 cm ^{3 of} water and 150 cm ^{3 of} dichloromethane were added to it. The aqueous phase is separated by decantation and reextracted 2 times with 50 cm ^{3 of} dichloromethane. The organic phases are combined, washed 3 times with 75 cm ^{3 of} water, dried on magnesium sulfate, filtered, then concentrated to dryness under reduced pressure (2.7 kPa) and at 40 ^o C. After recrystallization in ethyl acetate, 10.4 g N - / 2- (3,3-dimethylpiperidino) -carbonylphenyl / -2-phthalimidoacetamide, melting at 158 ^o C.

2- [3,3-Dimethylpiperidino] -carbonylamylin can be prepared as follows. To a suspension containing 51.6 g of dihydrated chloride of divalent tin in 64 cm ³ 6 N. an aqueous solution of hydrochloric acid, 16.7 g of 2- / 3,3-dimethylpiperidino / -carbonylnitrobenzene are added, maintaining the temperature at 40 ^° C. Then the reaction mixture is heated at a temperature close to 85 ^° C for 1 hour and 30 minutes , then cooled to a temperature close to 20 ^o C, and poured into a mixture consisting of 300 cm ^{3 of} water and 250 cm ^{3 of} dichloromethane, which is cooled to a temperature close to 0 ^o C. The mixture is alkalinized by adding 11 N. aqueous ammonia to a pH close to 9. The aqueous phase is separated by decantation and re-extracted 2 times with 100 cm ^{3 of} dichloromethane. The organic phases are combined, washed 4 times with 100 cm ^{3 of} water, dried on magnesium sulfate, filtered, then concentrated to dryness under reduced pressure (2.7 kPa) and at 40 ^o C. This gives 14.2 g 2- / 3, 3-dimethylpiperidino / β-carbonylaniline in the form of a liquid oil, used as it is, for subsequent syntheses.

2- [3,3-Dimethylpiperidino] -carbonylnitrobenzene can be prepared as follows. To a solution containing 7.9 g of 3,3-dimethylpiperidine and 7.7 g of triethylamine in 100 cm ^{3 of} dichloromethane is added at a temperature close to 15 ^° C., a solution containing 13.6 g of 2-nitrobenzene chloride in 25 cm ^{3 of} dichloromethane . The suspension is stirred for 2 hours at a temperature close to 20 ^o C, then poured into a mixture consisting of 75 cm ^{3 of} water and 100 cm ^{3 of} dichloromethane. The aqueous phase is separated by decantation and reextracted 2 times with 50 cm ^{3 of} dichloromethane. The organic phases are combined, washed 3 times with 30 cm ³ , then with 30 cm ³ 1 N. an aqueous solution of hydrochloric acid and 3 times 25 cm ^{3 of} water, dried on magnesium sulfate, filtered, then concentrated to dryness under reduced pressure (2.7 kPa) and at 40 ^o C. Thus, 16.8 g of 2- / 3 are obtained, 3-dimethylpiperidino / -carbonylnitrobenzene in the form of a liquid oil, used as it is for subsequent syntheses.

PRI me R 28. Carrying out the synthesis by a method similar to that described in example 27, but based on 2.5 g of 2 - {- 2-amino-N- [2 (N-methylanilino) -carbonylphenyl] - acetamido} -tert-butyl acetate and 0.83 g of 3-methylphenyl isocyanate, obtained after recrystallization in ethyl acetate, 1.9 g of 2 - {- N- [2- (N-methylanilino) -carbonylphenyl] -2- [3- (3 methylphenyl) ureido] acetamido} tert-butyl acetate melting at 145 ^° C.

 2- {2-amino-N- [2- (N-methylanilino) -carbonylphenyl / -acetamido} -tert-butyl acetate can be obtained by a method similar to that described in example 27 to obtain 2- {2-amino N- / 2- (3,3-dimethylpiperidino) -carbonylphenyl / -acetamido} -tert-butyl acetate, but starting from 3.3 g of 2- {N- / 2- (N-methylanilino) -carbonylphenyl / -2-phthalimidoacetamido } tert-butyl acetate and 0.93 g of hydrazine hydrate. Thus, 2.5 g of 2- {2-amino-N- [2- (N-methylanilino) -carbonylphenyl / acetamido} -tert-butyl acetate are obtained in the form of a liquid oil, used as it is for subsequent syntheses.

2- {N- / 2- (N-Methylanilino) -carbonylphenyl / -2-phthalimidoacetamido} tert-butyl acetate can be obtained by a method similar to that described in example 27 to obtain 2- {N- / 2- ( 3,3-dimethylpiperidino) -carbonylphenyl / 2-phthalimidoacetamido} -tert-butyl acetate, but starting from 8.3 g of N- / 2- (N-methylanilino) -carbonylphenyl / -2-phthalimidoacetamide, 1.1 g of hydride oil suspension sodium (50 wt.) and 4.5 g of tert-butyl bromoacetate. After recrystallization in ethyl acetate, 3.4 g of 2- {N- / 2- (N-methylanilino) -carbonylphenyl / -2-phthalimidoacetamido) tert-butyl acetate melting at 160 ^° C. are thus obtained.

N- / 2- (N-Methylanilino) -carbonylphenyl / -2-phthalimidoacetamide can be obtained by a method similar to that described in example 27 to obtain N- / 2- (3,3-dimethylpiperidino) -carbonylphenyl / -2 -phthalimidoacetamide, but starting from 6.8 g of 2- (N-methylanilino) -carbonylaniline, 3.3 g of triethylamine and 6.8 g of 2-phthalimidoacetyl chloride. After recrystallization in ethyl acetate, 10.8 g of N- / 2- (N-methylanilino) -carbonylphenyl / -2-phthalimidoacetamide, melting at 138 ^° C., are thus obtained.

2- (N-Methylanilino) -carbonylaniline can be obtained by a method similar to that described in example 27 to obtain 2- / 3,3-dimethylpiperidino / -carbonylaniline, but starting from 50 g of dihydrogen chloride of divalent tin, 70 cm ³ 6 n. an aqueous solution of hydrochloric acid and 17.5 g of 2- (N-methylanilino) -carbonylnitrobenzene. After recrystallization in diisopropyl ether, 10.3 g of 2- (N-methylanilino) -carbonylaniline are thus obtained, melting at 127 ^° C.

 2- (N-Methylanilino) -carbonylnitrobenzene can be obtained by a method similar to that described in example 27 to obtain 2- / 3,3-dimethylpiperidino / -carbonylnitrobenzene, but starting from 7.2 g of N-methylaniline, 7, 7 g of triethylamine and 13.6 g of 2-nitrobenzoyl chloride. Thus, 17.7 g of 2- (N-methylanilino) -carbonylnitrobenzene are obtained in the form of a liquid oil, used as it is for subsequent syntheses.

PRI me R 29. Carrying out the synthesis according to the method similar to that described in example 27, but starting from 2 g of 2- {2-amino-N- [1,2,3,4-tetrahydro-1-quinolyl ) -carbonylphenyl] -acetamido} -tert-butyl acetate and 0.63 g of 3-methylphenyl isocyanate, obtained after recrystallization in ethyl acetate, 1.2 g of 2- {2- [3- (3-methylphenyl) -ureido] -N-2 - (1,2,3,4-tetrahydro-1-quinolyl) -carbonylphenyl] -acetamido} -tert-butyl acetate, melting at 160 ^o C.

 2- {2-amino-N- [2- (2,2,3,4-tetrahydro-1-quinolyl) -carbonylphenyl] -acetamido} tert-butyl acetate can be obtained by a method similar to that described in example 27 to obtain 2- {2-amino-N- / 2- (3,3-dimethylpiperidino) -carbonylphenyl / acetamido} tert-butyl acetate, but starting from 4.4 g of 2- {2-phthalimido-N- [ 2- (1,2,3,4-tetrahydro-1-quinolyl) -carbonylphenyl] acetamido} tert-butyl acetate and 1.2 g of hydrazine hydrate. Thus, 2.1 g of 2- {2-amino-N- [2- (1,2,3,4-tetrahydro-1-quinolyl) -carbonylphenyl] acetamido} tert-butyl acetate are obtained in the form of a liquid oil used as it is, for subsequent syntheses.

2- {2-Phthalimido-N- / 2- (1,2,3,4-tetrahydro-1-quinolyl) -carbonylphenyl / - acetamido} tert-butyl acetate can be obtained by a method similar to that described in example 27 to obtain 2- {N- / 2- (3,3-dimethylpiperidino) -carbonylphenyl / -2-phthalimidoacetamido} -tert-butyl acetate, but starting from 31.5 g of 2-phthalimido-N- / 2- (1, 2,3,4-tetrahydro-1-quinolyl) -carbonylphenyl / -acetamide, 3.75 g of an oil suspension of sodium hydride (50 wt.) And 16.1 g of bromine tert-butyl acetate. After recrystallization in ethyl acetate, 26.5 g of 2- {2-phthalimido-N- / 2- (1,2,3,4-tetrahydro-1-quinolyl) -carbonylphenyl / -acetamido} -tert-butyl acetate, melting, are thus obtained. at 150 ^o C.

2-Phthalimido-N- / 2- (1,2,3,4-tetrahydro-1-quinolyl) -carbonylphenyl / -acetamide can be obtained by a method similar to that described in example 27 to obtain 2-phthalimido-N - / 2- (3,3-dimethylpiperidino) -carbonylphenyl / -acetamide, but starting from 20.2 g of 2- / 1,2,3,4-tetrahydro-1-quinolyl / -carbonylaniline, 9.1 g of triethylamine and 19.7 g of 2-phthalimidoacetyl chloride. After recrystallization in ethyl acetate, 31.6 g of 2-phthalimido-N- / 2- (1,2,3,4-tetrahydro-1-quinolyl) -carbonylphenyl / -acetamide are obtained, melting at 130 ^° C.

2- / 1,2,3,4-Tetrahydro-1-quinolyl / -carbonylaniline can be obtained by a method similar to that described in example 27 to obtain 2- / 3,3-dimethylpiperidino / -carbonylaniline, but starting from 114 g of dihydrated chloride of divalent tin, 140 cm ³ 6 N. an aqueous solution of hydrochloric acid and 39.7 g of 2- / 1,2,3,4-tetrahydro-1-quinolyl / -carbonylnitrobenzene. After recrystallization in ethyl acetate, 20.2 g of 2- [1,2,3,4-tetrahydro-1-quinolyl] -carbonylaniline melting at 102 ^° C. are thus obtained.

2- / 1,2,3,4-Tetrahydro-1-quinolyl / -carbonylnitrobenzene can be obtained by a method similar to that described in example 27 to obtain 2- / 3,3-dimethylpiperidino / -carbonylnitrobenzene, but starting from 20 g of 1,2,3,4-tetrahydroquinolyl, 16.5 g of triethylamine and 29.7 g of 2-nitrobenzene chloride. After recrystallization in ethyl acetate, 39.7 g of 2- (1,2,3,4-tetrahydro-1-quinolyl) -carbonylnitrobenzene melting at 155 ^° C. are thus obtained.

PRI me R 30. To a solution containing 2.6 g of 2- / 2-amino-N- (2-anilinophenyl) -acetamido / -tert-butyl acetate in 20 cm ^{3 of} anhydrous tetrahydrofuran is added at a temperature close to 20 ^o C, 1.07 g of 3-methylphenyl isocyanate. The resulting solution was stirred for 2 hours at a temperature close to 20 ^o C, then concentrated to dryness under reduced pressure (2.7 kPa) and at 40 ^o C. The residual liquid oil was purified by chromatography on 150 g of silica (0.063-0.2 mm) located in a column with a diameter of 2 cm (eluent: cyclohexane-ethyl acetate (50:50 by volume)), collecting fractions of 20 cm ³ . Fractions containing only the desired product are combined and concentrated to dryness under reduced pressure (2.7 kPa) and at 40 ^° C. After recrystallization in ethyl acetate, 1.15 g of 2- {N- / 2-anilinophenyl / -2- / 3 is obtained - (3-methylphenyl) -ureido / acetamido} -tert-butyl acetate, melting at 180 ^o C.

2/2-amino-N- (2-anilinophenyl) acetamido / tert-butyl acetate can be prepared as follows. To a solution containing 4.2 g of 2- / N- (2-anilinophenyl) -2-phthalimidoacetamido / t-butyl acetate in 100 cm ^{3 of} methanol, 1.3 g of hydrazine hydrate was added. The reaction mixture is stirred for 5 hours at a temperature close to 20 ^° C., then concentrated to dryness under reduced pressure (2.7 kPa) and at 40 ^° C. The residue is taken up with 200 cm ^{3 of} diethyl ether and the insoluble product is separated by filtration. . The filtrate is concentrated to dryness under reduced pressure (2.7 kPa) and at 40 ^° C. 2.6 g of 2- / 2-amino-N- (2-anilinophenyl) acetamido / tert-butyl acetate are thus obtained in the form of a liquid oil used as it is for subsequent syntheses.

2- / N- (2-Anilinophenyl) -2-phthalimidoacetamido / tert-butyl acetate can be prepared as follows. To the solution maintained under an atmosphere of argon containing 8.7 g of N- / 2-analinofenil / -2-phthalimidoacetamide in 100 cm ³ of anhydrous tetrahydrofuran is added at a temperature close to 10 ^o C, 1,1 g of an oil suspension of sodium (50 wt .) and the resulting suspension is stirred for 1 h at a temperature close to 20 ^° C. Then a solution containing 4.6 g of tert-butyl bromoacetate in 20 cm ^{3 of} anhydrous tetrahydrofuran is added and stirring is continued for 3 hours at a temperature close to 20 ^o C. The reaction mixture was then poured into a chilled to a temperature near th to 0 ^o C, a mixture consisting of 100 cm ³ of water and 200 cm ³ of ethyl acetate. The aqueous phase is separated by decantation and reextracted 2 times with 20 cm ^{3 of} ethyl acetate. The organic phases are combined, washed 3 times with 25 cm ^{3 of} water, dried on magnesium sulfate, filtered, then concentrated to dryness under reduced pressure (2.7 kPa) and at 40 ^o C. Thus, 4.2 g of 2- / N- (2-anilinophenyl) -2-phthalimidoacetamido / -acetate tert-butyl, melting at 205 ^o C.

N- / 2-Anilinophenyl / -2-phthalimidoacetamide can be prepared as follows. To a solution aged in an argon atmosphere containing 9.2 g of N-phenyl-1,2-diaminobenzene and 5.1 g of triethylamine in 60 cm ^{3 of} dichloromethane, a solution containing 11.2 g was added while maintaining the temperature at 20 ^° C. 2-phthalimidoacetyl chloride in 60 cm ^{3 of} dichloromethane. The resulting solution was stirred for 2 hours at a temperature close to 20 ^o C, then 100 cm ^{3 of} water was added to it. The aqueous phase is separated by decantation, then reextracted 2 times with 50 cm ^{3 of} dichloromethane. The organic phases are combined, washed 2 times with 30 cm ^{3 of} water, dried on magnesium sulfate, filtered, then concentrated to dryness under reduced pressure (2.7 kPa) and at 40 ^o C. After recrystallization in ethyl acetate, 8.8 g N - / 2-anilinophenyl / -2-phthalimidoacetamide, melting at 191 ^o C.

PRI me R 31. To a solution maintained in an argon atmosphere containing 1.1 g of 3- / 1-hydroxyethyl / -aniline in 20 cm ^{3 of} anhydrous tetrahydrofuran, 3 g of 2- was added at a temperature close to 20 ^o C / N- (3-methoxyphenyl) isocyanatoacetamido / -N-methyl-N-phenylacetamide. The resulting solution was stirred for 16 hours at a temperature close to 20 ^o C, then concentrated to dryness under reduced pressure (2.7 kPa) and at 40 ^o C. The residual liquid oil was purified by chromatography on 150 g of silica (0.063-0.2 mm) located in a column with a diameter of 2.5 cm (eluent: dichloromethane-methanol (98: 2 by volume)), collecting fractions of 20 cm ³ . Fractions containing only the desired product are combined and concentrated to dryness under reduced pressure (2.7 kPa) and at 40 ^° C. After recrystallization in diisopropyl ether, 1.7 g of 2- {2- [3- / 3- (1- hydroxyethyl) -phenyl / -ureido] -N- / 3-methoxyphenyl / -acetamido} -N-methyl-N-phenylacetamide- / RS /, melting at 115 ^o C.

PRI me R 32. Carrying out the synthesis according to a method similar to that described in example 31, but based on 0.86 g of 3- / 1-hydroxyethyl / aniline and 2.8 g of 2- / N- (2 -ethoxycarbonylphenyl) -isocyanatoacetamido / -N-methyl-N-phenylacetamide, obtained after recrystallization in ethyl acetate, 2 g of 2- {2- [3- / 3- (1-hydroxyethyl) -phenyl / -ureido] -N- / 2- ethoxycarbonylphenyl / -acetamido} -N-methyl-N-phenylacetamide, melting at 195 ^o C.

 2- / N- (2-Ethoxycarbonylphenyl) -isocyanatoacetamido / -N-methyl-N-phenylacetamide can be obtained by a method similar to that described in example 26 to obtain 2- / N- (3-methoxyphenyl) -isocyanatoacetamido / -N-methyl-N-phenylacetamide, but starting from 1.1 g of isocyanatoacetyl chloride, 2.2 g of 2- / 2-ethoxycarbonylphenyl / amino-N-methyl-N-phenylacetamide and 0.65 g of pyridine. 8 g of 2- / N- (2-ethoxycarbonylphenyl) -isocyanatoacetamido / -N-methyl-N-phenylacetamide in the form of a liquid oil, used as it is for subsequent syntheses.

2- (2-Ethoxycarbonylphenyl) -amino-N-methyl-N-phenylacetamide can be obtained by a method similar to that described in example 26 to obtain 2- / 3-methoxyphenyl / -amino-N-methyl-N-phenylacetamide but based on 3.1 g of 2- / N- (2-ethoxycarbonylphenyl) trifluoroacetamido / -N-methyl-N-phenylacetamide and 7.5 cm ³ 2 N. an aqueous solution of sodium hydroxide. Thus, 2.2 g of 2- [2-ethoxycarbonylphenyl] -amino-N-methyl-N-phenylacetamide melting at 100 ^° C.

2- / N- (2-Ethoxycarbonylphenyl) trifluoroacetamido / -N-methyl-N-phenylacetamide can be obtained by a method similar to that described in example 26 to obtain 2- / N- (3-methoxyphenyl) trifluoroacetamido / -N-methyl-N-phenylacetamide, but starting from 5.8 g of ethyl 2-trifluoroacetylaminobenzoate and 1.3 g of an oil suspension of sodium hydrate (50 wt.) And 7.3 g of bromo-N-methyl-N-phenylacetamide. Thus, 5.7 g of 2- / N- (2-ethoxycarbonylphenyl) trifluoroacetamido / -N-methyl-N-phenylacetamide, melting at 95 ^° C., is obtained.

Ethyl 2-trifluoroacetylaminobenzoate can be prepared by a method analogous to that described in Example 26 for the preparation of N- / 3-methoxyphenyl / trifluoroacetamide, but starting from 4.1 g of ethyl 2-aminobenzoate and 5.3 g of trifluoroacetic anhydride. Thus, 6.4 g of ethyl 2-trifluoroacetylamino-benzoate is obtained, melting at 78 ^° C.

PRI me R 33. Carrying out the synthesis according to the method similar to that described in example 31, but based on 0.86 g of 3-hydroxymethylaniline and 2.9 g of 2- / N- (2-ethoxycarbonylphenyl) -isocyanatoacetamido / -N-methyl-N-phenylacetamide, obtained after recrystallization in ethyl acetate 2 - {- N- / 2-ethoxycarbonylphenyl / -2- / 3- (3-hydroxymethylphenyl) ureido / - acetamido} -N-methyl-N-phenylacetamide melting at 184 ^o C.

PRI me R 34. Carrying out the synthesis according to the method similar to that described in example 31, but based on 1.1 g of 3-hydroxymethylaniline and 3.2 g of 2- / N- (3-methoxyphenyl) -isocyanatoacetamido / -N-methyl-N-phenylacetamide, 2.6 g of 2- {2- / 3- (3-hydroxymethylphenyl) -ureido / -N- / 3-methoxyphenyl / acetamido} -N-methyl- are obtained after recrystallization in ethyl acetate N-phenylacetamide, melting at 142 ^o C.

PRI me R 35. Carrying out the synthesis according to a method similar to that described in example 27, but based on 3.1 g of 2- / 2-amino-N- (3-ethoxycarbonylphenyl) -acetamido / -N-methyl -N-phenylacetamide and 1.2 g of 3-methylphenyl isocyanate, obtained after recrystallization in diisopropyl ether, 2 g of 2- {N- / 3-ethoxycarbonylphenyl / -2- / 3- (3-methylphenyl) -ureido / -acetamido} - N-methyl-N-phenylacetamide, melting at 88 ^o C.

 2- / 2-amino-N- (3-ethoxycarbonylphenyl) -acetamido / -N-methyl-N-phenylacetamide can be obtained by a method similar to that described in example 27 to obtain 2- {2-amino-N- / 2- (3,3-dimethylpiperidino) -carbonylphenyl / -acetamido} -tert-butyl acetate, but starting from 4.2 g of 2- / N- (3-ethoxycarbonylphenyl) -2-phthalimidoacetamido / -N-methyl-N- phenylacetamide and 1.25 g of hydrazine hydrate. Thus, 3 g of 2- / 2-amino-N- (3-ethoxycarbonylphenyl) -acetamido / -N-methyl-N-phenylacetamide are obtained in the form of a liquid oil, used as it is for subsequent syntheses.

 2- / N- (3-Ethoxycarbonylphenyl) -2-phthalimidoacetamido / -N-methyl-N-phenylacetamide can be obtained by a method similar to that described in example 27 to obtain 2- {N- / 2-3,3 -dimethylpiperidino) -carbonylphenyl / -2-phthalimidoacetamido} -tert-butyl acetate, but based on 3.9 g of N- (3-ethoxycarbonylphenyl / -2-phthalimidoacetamide, 0.64 g of an oily suspension of sodium hydride (50 wt.) and 3 3 g of 2-bromo-N-methyl-N-phenylacetamide 4.2 g of 2- / N- (3-ethoxycarbonylphenyl) -2-phthalimidoacetamido / -N-methyl-N-phenylacetamide are thus obtained.

N- / 3-Ethoxycarbonylphenyl / -2-phthalimidoacetamide can be obtained by a method similar to that described in example 27 to obtain N- / 2- (3,3-dimethylpiperidino) -carbonylphenyl / -2-phthalimidoacetamide, but starting from 5 g of ethyl 3-aminobenzoate, 3.9 g of triethylamine and 8.1 g of 2-phthalimidoacetyl chloride. After recrystallization in ethyl acetate, 8.7 g of N- [3-ethoxycarbonylphenyl] -2-phthalimidoacetamide, melting at 215 ^° C., are thus obtained.

PRI me R 36. Carry out the synthesis according to a method similar to that described in example 26, but based on 0.5 g of 3- {N- / N-methyl-N-phenylcarbamylmethyl / -2- / 3- ( 3-methylphenyl) -ureido / acetamido} ethylbenzoate and 1 cm ³ 1 N. an aqueous solution of sodium hydroxide. Thus, 0.3 g of 3- {N- / N-methyl-N-phenylcarbamylmethyl / -2- / 3- (3-methylphenyl) -ureido / -acetamido} -benzoic acid, melting at 140 ^° C., is obtained.

PRI me R 37. The synthesis is carried out by a method similar to that described in example 26, but based on 2.45 g of 3- {3- / N- (3-methoxyphenyl) -N- (N-methyl- N-phenylcarbamylmethyl) -carbamylmethyl / -ureido} phenylethyl acetate and 4.6 cm ³ 1 N an aqueous solution of sodium hydroxide. Thus, 1.6 g of 3- {3- / N- (3-methoxyphenyl) -N- (N-methyl-N-phenylcarbamylmethyl) -carbamylmethyl / -ureido} phenylacetic acid, melting at 120 ^° C., is obtained.

3- {3- / N- (3-Methoxyphenyl) -N- (N-methyl-N-phenylcarbamylmethyl) -carbamylmethyl / - ureido} phenylethyl acetate can be obtained by the method similar to that described in example 26 to obtain 3 - {3- / N- (3-methoxyphenyl) -N- (N-methyl-N-phenylcarbamylmethyl) -carbamylmethyl / -ureido) ethylbenzoate, but starting from 2.4 g of 2- / N- (3-methoxyphenyl) -isocyanatoacetamido / -N-methyl-N-phenylacetamide and 1.1 g of 3-aminophenylethyl acetate. The crude product is purified by chromatography on 60 silica (0.063-0.2 mm) located in a column with a diameter of 2.0 cm (eluent: dichloromethane-ethyl acetate (20:80 by volume)), collecting fractions of 20 cm ³ . Fractions 8 to 18 are combined and concentrated to dryness under reduced pressure (2.7 kPa) and at 40 ^° C. 2.45 g of 3- {3- / N- (3-methoxyphenyl) -N- (N- methyl-N-phenylcarbamylmethyl) -carbamylmethyl / - ureido} phenylethyl acetate in the form of an amorphous powder, used as it is for subsequent syntheses.

3-aminophenylethyl acetate can be prepared as follows. 0.1 g of palladium supported on activated carbon with a content of 5% was added to a solution containing 2.0 g of 3-nitrophenylethyl acetate in 20 cm ^{3 of} ethanol. The suspension was stirred for 2 hours at a temperature close to 25 ^o C in a hydrogen atmosphere (100 kPa). The catalyst is separated by filtration, and the filtrate is concentrated to dryness under reduced pressure (2.7 kPa) and at 40 ^° C. 1.7 g of 3-aminophenylethyl acetate are thus obtained in the form of a liquid oil, used as it is for subsequent syntheses.

 Ethyl 3-nitrophenyl acetate can be obtained by the method described in Segers et A. Bruylants, Bul. Soc. Chim. Belg. 64, 87 (1955).

PRI me R 38. To a solution maintained in a nitrogen atmosphere containing 1.2 g of boron tribromide in 20 cm ^{3 of} dichloromethane, at a temperature close to -55 ^o C, a suspension containing 0.8 g 3 was added over 5 minutes - {3- [N- (3-methoxyphenyl) -N- (N-methyl-N-phenylcarbamylmethyl) -carbamylmethyl / - ureido} phenylacetic acid in 15 cm ^{3 of} dichloromethane. The resulting mixture was stirred for 15 minutes at a temperature close to -55 ^o C, then for 20 hours at a temperature close to 20 ^o C. Then add 20 cm ³ water, then 5 cm ³ 1 N. an aqueous solution of sodium hydroxide. The organic phase is separated by decantation, the aqueous phase is washed 2 times with 20 cm ³ ethyl acetate, then acidified with 5 cm ³ 1 N. an aqueous solution of hydrochloric acid. The precipitate formed is filtered off, washed 3 times with 5 cm ^{3 of} water and dried in air. Thus, 0.3 g of 3- {3- / N- (3-hydroxyphenyl) -N- (N-methyl-N-phenylcarbamylmethyl) -carbamylmethyl / -ureido} phenylacetic acid, melting at a temperature of 148 ^° C., is obtained.

PRI me R 39. Carrying out the synthesis according to the method similar to that described in example 1, but starting from 1.2 g of 2- / 2-amino-N- (2-methylphenyl) -acetamido / -N-methyl -N-phenylacetamide and 1.3 g of 3-methylphenyl isocyanate, 2.3 g of 2- {N- / 2-methylphenyl / -2- / 3-methylphenyl) -ureido / -acetamido} -N- are obtained after recrystallization in ethyl acetate methyl N-phenylacetamide melting at 193 ^o C.

 2- / 2-amino-N- (2-methylphenyl) -acetamido / -N-methyl-N-phenylacetamide can be obtained by a method similar to that described in example 4 to obtain 2- / 2-amino-N- (2-trifluoromethoxyphenyl) -acetamido / -tert-butyl acetate, but starting from 5.3 g of 2- / N- (2-methylphenyl) -2-phthalimidoacetamido / -N-methyl-N-phenylacetamide and 1.2 g of hydrazine hydrate . Thus, 3.8 g of 2- [2-amino-N- (2-methylphenyl) -acetamido] -N-methyl-N-phenylacetamide are obtained in the form of a liquid oil, used as it is for subsequent syntheses.

2- / N- (2-Methylphenyl) -2-phthalimidoacetamido / -N-methyl-N-phenylacetamide can be obtained by a method similar to that described in example 4 to obtain 2- / 2-phthalimido-N- (2 -trifluoromethoxyphenyl) -acetamido / -tert-butyl acetate, but based on 5.9 g of N- / 2-methylphenyl / -2-phthalimidoacetamide, 1.15 g of an oily suspension of sodium hydride (50 wt.) and 6.8 g of 2- bromo-N-methyl-N-phenylacetamide. After recrystallization in diisopropyl ether, 7.1 g of 2- / N- (2-methylphenyl) -2-phthalimidoacetamido / -N-methyl-N-phenylacetamide melting at 120 ^° C. are thus obtained.

N- / 2-Methylphenyl / - 2-phthalimidoacetamide can be obtained by a method similar to that described in example 4 to obtain 2-phthalimido-N- / 2-trifluoromethoxyphenyl / -acetamide, but based on 5.4 g of 2- methylaniline, 6.6 g of triethylamine and 13.4 g of 2-phthalimidoacetyl chloride. After recrystallization in ethyl acetate, 14.4 g of N- / 2-methylphenyl / -2-phthalimidoacetamide are thus obtained, melting at 254 ^° C.

PRI me R 40. Carrying out the synthesis according to the method similar to that described in example 1, but based on 2.0 g of 2- / 2-amino-N- (2-methoxyphenyl) -acetamido / -N-methyl -N-phenylacetamide and 0.64 g of 3-methylphenyl isocyanate, obtained after recrystallization in ethyl acetate, 1.5 g of 2- {N- / 2-methoxyphenyl / -2- / 3- (3-methylphenyl) -ureido / -acetamido} -N-methyl-N-phenylacetamide, melting at 212 ^o C.

 2- / 2-amino-N- (2-methoxyphenyl) -acetamido / -N-methyl-N-phenylacetamide can be obtained by a method similar to that described in example 4 to obtain 2- / 2-amino-N- (2-trifluoromethoxyphenyl) -acetamido / tert-butyl acetate, but starting from 4.0 g of 2- / N- (2-methoxyphenyl) -2-phthalimidoacetamido / -N-methyl-N-phenylacetamide and 1.3 g of hydrazine hydrate . Thus, 2.0 g of 2- / 2-amino-N- (2-methoxyphenyl) -acetamido / -N-methyl-N-phenylacetamide is obtained in the form of a liquid oil, used as it is for subsequent syntheses.

2-N- (2-Methoxyphenyl) -2-phthalimidoacetamido / -N-methyl-N-phenylacetamide can be obtained by a method similar to that described in example 4 to obtain 2- / 2-phthalimido-N- (2- trifluoromethoxyphenyl) -acetamido / -tert-butyl acetate, but starting from 6.2 g of N- / 2-methoxyphenyl / -2-phthalimidoacetamide, 1.15 g of an oil suspension of sodium hydride (50 wt.) and 6.8 g of 2-bromine -N-methyl-N-phenylacetamide. After recrystallization in ethyl acetate, 5.1 g of 2- / N- (2-methoxyphenyl) -2-phthalimidoacetamido / -N-methyl-N-phenylacetamide melting at 199 ^° C are thus obtained.

N- / 2-Methoxyphenyl / -2-phthalimidoacetamide can be obtained by a method similar to that described in example 4 to obtain 2-phthalimido-N- / 2-trifluoromethoxyphenyl / -acetamide, but based on 6.7 g of 2- methoxyaniline, 6.6 g of triethylamine and 13.4 g of 2-phthalimidoacetyl chloride. After recrystallization in acetonitrile, 14.6 g of N- / 2-methoxyphenyl / -2-phthalimidoacetamide are thus obtained, melting at 211 ^° C.

PRI me R 41. Carrying out the synthesis according to the method similar to that described in example 1, but based on 4.7 g of 2- / 2-amino-N- (2-phenoxyphenyl) -acetamido / -tert-butyl acetate and 1.9 g of 3-methylphenyl isocyanate, 1.7 g of 2- {2- / 3- (3-methylphenyl) -ureido / -N- / 2-phenoxyphenyl / -acetamido} -tert-butyl acetate are obtained after recrystallization in ethyl acetate melting at 204 ^o C.

 2- / 2-amino-N- (2-phenoxyphenyl) -acetamido / -tert-butyl acetate can be obtained by the method similar to that described in example 4 to obtain 2- / 2-amino-N- (2-trifluoromethoxyphenyl ) -acetamido / tert-butyl acetate, but starting from 6.3 g of 2- / N- (2-phenoxyphenyl) -2-phthalimidoacetamido / tert-butyl acetate and 2 g of hydrazine hydrate. Thus, 4.7 g of 2- / 2-amino-N- (2-phenoxyphenyl) -acetamido / -tert-butyl acetate are obtained in the form of a liquid oil, used as it is for subsequent syntheses.

2- / N- (2-Phenoxyphenyl) -2-phthalimidoacetamido / tert-butyl acetate can be obtained by a method similar to that described in example 4 to obtain 2- / 2-phthalimido-N- (2-trifluoromethoxyphenyl) - acetamido / tert-butyl acetate, but starting from 7.5 g of N- / 2-phenoxyphenyl / -2-phthalimidoacetamide, 1.1 g of an oily suspension of sodium hydride (50 wt.) and 4.3 g of bromo-tert-butyl acetate. Thus, 7.1 g of 2- / N- (2-phenoxyphenyl) -2-phthalimidoacetamido / tert-butyl acetate are obtained, melting at 145 ^° C.

N- / 2-Phenoxyphenyl / -2-phthalimidoacetamide can be obtained by a method similar to that described in example 4 to obtain 2-phthalimido-N- (2-trifluoromethoxyphenyl) -acetamide, but starting from 4.6 g of 2- phenoxyaniline, 2.5 g of triethylamine and 5.6 g of 2-phthalimidoacetyl chloride. Thus, 8.3 g of N- / 2-phenoxyphenyl / -2-phthalimidoacetamide melting at 143 ^° C. are obtained.

PRI me R 42. Carrying out the synthesis according to the method similar to that described in example 1, but based on 5.8 g of 2- / 2-amino-N- (2-biphenylyl) -acetamido / -acetate tert- butyl and 2.3 g of 3-methylphenyl isocyanate, obtained after recrystallization in ethyl acetate, 3.7 g of 2- {N- / 2-biphenylyl / -2- / 3- (3-methylphenyl) -ureido / acetamido} -tert-butyl acetate melting at 177 ^o C.

 2- / 2-amino-N- (2-biphenylyl) -acetamido / tert-butyl acetate can be obtained by a method similar to that described in example 4 to obtain 2- / 2-amino-N- (2-trifluoromethoxyphenyl ) -acetamido / tert-butyl acetate, but starting from 7.5 g of 2- / N- (2-biphenylyl) -2-phthalimidoacetamido / tert-butyl acetate and 2.4 g of hydrazine hydrate. Thus, 5.8 g of 2- / 2-amino-N- (2-biphenylyl) -acetamido / tert-butyl acetate is obtained in the form of a liquid oil, which is used as it is for subsequent syntheses.

2- / N- (2-Biphenylyl) -2-phthalimidoacetamido / tert-butyl acetate can be obtained by a method similar to that described in example 4 to obtain 2- / 2-phthalimido-N- (2-trifluoromethoxyphenyl) - acetamido / tert-butyl acetate, but starting from 6.5 g of N- / 2-biphenylyl / -2-phthalimidoacetamide, 0.87 g of an oil suspension of sodium hydride (50% by weight) and 3.6 g of tert-butyl bromoacetate. Thus, 8 g of 2- / N- (2-biphenylyl) -2-phthalimidoacetamido / tert-butyl acetate are obtained, melting at 145 ^° C.

N- (2-biphenylyl) -2-phthalimidoacetamide can be obtained by a method similar to that described in example 4 to obtain 2-phthalimido-N- / 2-trifluoromethoxyphenyl / -acetamide, but based on 4.2 g of 2- aminobiphenyl, 2.7 g of triethylamine and 5.6 g of 2-phthalimidoacetyl chloride. 7.1 g of 2-phthalimido-N- [2-biphenylyl] -acetamide melting at 204 ^° C. are thus obtained.

PRI me R 43. Carrying out the synthesis according to a method similar to that described in example 1, but based on 8.1 g of 2- / 2-amino-N- (2-benzylphenyl) -acetamido / -tert-butyl acetate and 3 g of 3-methylphenyl isocyanate, 6.6 g of 2 - {- N- / 2-benzylphenyl / -2- / 3- (3-methylphenyl) -ureido / -acetamido} -tert-butyl acetate are obtained after recrystallization in ethyl acetate, melting at 183 ^o C.

 2- / 2-amino-N- (2-benzylphenyl) -acetamido / -tert-butyl acetate can be obtained by the method similar to that described in example 4 to obtain 2- / 2-amino-N- (2-trifluoromethoxyphenyl ) -acetamido / tert-butyl acetate, but starting from 11.2 g of 2- / N- (2-benzylphenyl) -2-phthalimidoacetamido / tert-butyl acetate and 3.5 g of hydrazine hydrate. Thus, 8.1 g of 2- / 2-amino-N- (2-benzylphenyl) -acetamido-tert-butyl acetate are obtained in the form of a liquid oil, used as it is for subsequent syntheses.

2- / N- (2-Benzylphenyl) -2-phthalimido-acetamido / -tert-butyl acetate can be obtained by a method similar to that described in example 4 to obtain 2- / 2-phthalimido-N- (2-trifluoromethoxyphenyl ) -acetamido / -tert-butyl acetate, but starting from 9.3 g of N- / 2-benzylphenyl / -2-phthalimidoacetamide, 1.4 g of an oil suspension of sodium hydride (50 wt.) and 5.9 g of bromo-tert-butyl butyl acetate. Thus, 11.3 g of 2- / N- (2-benzylphenyl) -2-phthalimidoacetamido / tert-butyl acetate are obtained, melting at 190 ^° C.

N- / 2-Benzylphenyl / -2-phthalimidoacetamide can be obtained by a method similar to that described in example 4 to obtain 2-phthalimido-N- / 2-trifluoromethoxyphenyl / -acetamide, but starting from 4.6 g of 2- benzylaniline, 3 g of triethylamine and 7.3 g of 2-phthalimidoacetyl chloride. Thus, 9.3 g of N- / 2-benzylphenyl / -2-phthalimidoacetamide melting at 232 ^° C. are obtained.

PRI me R 44. Carrying out the synthesis according to the method similar to that described in example 1, but based on 3.3 g of 2- / 2-amino-N- (3-ethoxycarbonylphenyl) -acetamido / -tert-butyl acetate and 1.3 g of 3-methylphenyl isocyanate, obtained after recrystallization in diisopropyl ether, 0.85 g of 2- {N- / 3-ethoxycarbonylphenyl / -2- / 3- (3-methylphenyl) -ureido / -acetamido} -tret- butyl acetate, melting at 71 ^o C.

 2- / 2-amino-N- (3-ethoxycarbonylphenyl) -acetamido / tert-butyl acetate can be obtained by a method similar to that described in example 4 to obtain 2- / 2-amino-N- (2-trifluoromethoxyphenyl ) -acetamido / tert-butyl acetate, but starting from 5 g of 2- / N- (3-ethoxycarbonylphenyl) -2-phthalimidoacetamido / tert-butyl acetate and 1.6 g of hydrazine hydrate. Thus, 3.3 g of 2- / 2-amino-N- (3-ethoxycarbonylphenyl) -acetamido / tert-butyl acetate are obtained in the form of a liquid oil, used as it is for subsequent syntheses.

 2- / N- (3-ethoxycarbonylphenyl) -2-phthalimidoacetamido / tert-butyl acetate can be obtained by a method similar to that described in example 4 to obtain 2- / 2-phthalimido-N- (2-trifluoromethoxyphenyl) - acetamido / tert-butyl acetate, but starting from 6 g of N- / 3-ethoxycarbonylphenyl / -2-phthalimidoacetamide, 1 g of an oily suspension of sodium hydride (50 wt.) and 4 g of bromo-tert-butyl acetate. Thus, 5.1 g of 2- / N- (3-ethoxycarbonylphenyl) -2-phthalimidoacetamido / tert-butyl acetate are obtained in the form of a liquid oil, used as it is for subsequent syntheses.

N- / 3-Ethoxycarbonylphenyl / -2-phthalimidoacetamide can be obtained by a method similar to that described in example 4 to obtain 2-phthalimido-N- (2-trifluoromethoxyphenyl / -acetamide, but based on 3.3 g of 3- ethyl aminobenzoate, 2.4 g of triethylamine and 5.8 g of 2-phthalimidoacetyl chloride. Thus 6.2 g of N- / 3-ethoxycarbonylphenyl / -2-phthalimidoacetamide are obtained, melting at 219 ^° C.

PRI me R 45. Carrying out the synthesis according to the method similar to that described in example 1, but starting from 2.25 g of 2/2-amino-N- (2-ethoxycarbonylphenyl) -acetamido / -N-methyl- N-phenylacetamide and 0.88 g of 3-methylphenyl isocyanate, obtained after recrystallization in ethyl acetate, 1.6 g of 2- {N- / 2-ethoxycarbonylphenyl / -2- / 3- (3-methylphenyl) -ureido / -acetamido} - N-methyl-N-phenylacetamide, melting at 201 ^o C.

 2- / 2-amino-N- (2-ethoxycarbonylphenyl) -acetamido / -N-methyl-N-phenylacetamide can be obtained by the method similar to that described in example 4 to obtain 2- / 2-amino-N- (2-trifluoromethoxyphenyl) -acetamido / -tert-butyl acetate, but starting from 3.0 g of 2- / N- (2-ethoxycarbonylphenyl) -2-phthalimidoacetamido / -N-methyl-N-phenylacetamide and 0.9 g of hydrazine hydrate . 2.25 g of 2- [2-amino-N- (2-ethoxycarbonylphenyl) -acetamido / -N-methyl-N-phenylacetamide are thus obtained in the form of a liquid oil, used as such for the subsequent syntheses.

2- / N- (2-Ethoxycarbonylphenyl) -2-phthalimidoacetamido / -N-methyl-N-phenylacetamide can be obtained by a method similar to that described in example 4 to obtain 2- / 2-phthalimido-N- (2 -trifluoromethoxyphenyl) -acetamido / -tert-butyl acetate, but starting from 5.4 g of N- / 2-ethoxycarbonylphenyl / -2-phthalimidoacetamide, 0.9 g of an oily suspension of sodium hydride (50 wt.) and 5.25 g of 2- bromo-N-methyl-N-phenylacetamide. After recrystallization in ethyl acetate, 3.0 g of 2- / N- (2-ethoxycarbonylphenyl) -2-phthalimidoacetamido / -N-methyl-N-phenylacetamide melting at 202 ^° C. are thus obtained.

N- / 2-Ethoxycarbonylphenyl / -2-phthalimidoacetamide can be obtained by a method similar to that described in example 4 to obtain 2-phthalimido-N- / 2-trifluoromethoxyphenyl / -acetamide, but based on 4.1 g of 2- ethyl aminobenzoate, 2.8 g of triethylamine and 5.6 g of 2-phthalimidoacetyl chloride. After recrystallization in ethyl acetate, 8.7 g of N- [2-ethoxycarbonylphenyl] -2-phthalimidoacetamide, melting at 197 ^° C., are thus obtained.

PRI me R 46. Carrying out the synthesis according to the method similar to that described in example 27, but based on 2 g of 2- {2-amino-N- / 2- (N-methylanalino) -carbonylphenyl / -acetamido} -N-methyl-N-phenylacetamide and 0.62 g of 3-methylphenyl isocyanate, 1.45 g of 2- {N- [2- (N-methylanilino) -carbonylphenyl] -2- [3- (3-methylphenyl) is obtained -ureido] - acetamido} -N-methyl-N-phenylacetamide, melting at 140 ^o C.

 2- {2-amino-N- [2- (N-methylanilino) -carbonylphenyl / -acetamido} -N-methyl-N-phenylacetamide can be obtained by a method similar to that described in example 27 to obtain 2- { 2-amino-N- / 2- (3,3-dimethylpiperidino) -carbonylphenyl / -acetamido} tert-butyl acetate, but starting from 2.8 g of N-methyl-2 - {- N- / 2- (N- methylanilino) -carbonylphenyl / -2-phthalimido-acetamido} -N-phenylacetamide and 0.75 g of hydrazine hydrate. Thus, 2 g of 2- {2-amino-N- [2- (N-methylanilino) -carbonylphenyl / acetamido} -N-methyl-N-phenylacetamide are obtained in the form of a liquid oil, used as it is, for the subsequent syntheses.

N-Methyl-2- {N- / 2- (N-methylanilino) -carbonylphenyl / -2-phthalimidoacetamido} -N-phenylacetamide can be prepared as follows. To a suspension containing 8.3 g of N- / 2- (N-methylanilino) -carbonylphenyl / -2-phthalimidoacetamide and 3 g of potassium carbonate in 50 cm ^{3 of} N, N-dimethylformamide are added at a temperature close to 20 ^o C, a solution containing 4.6 of 2-bromo-N-methyl-N-phenylacetamide in 25 cm ³ N, N-dimethylformamide. The resulting mixture is stirred for 120 hours, then poured into 800 cm ^{3 of} water. The insoluble product is separated by filtration, washed 4 times with 100 cm ^{3 of} water, dried in air and purified by chromatography on 90 g of silica (0.04-0.063 mm) in a column with a diameter of 3.2 cm (eluent: dichloromethane), by collecting fractions of 50 cm ³ . Fractions 60 to 90 are combined and concentrated to dryness under reduced pressure (2.7 kPa) and at 50 ^° C. 2.8 g of N-methyl-2- {N- / 2- (N-methylanilino) -carbonylphenyl are thus obtained. / -2-phthalimidoacetamido} -N-phenylacetamide as an amorphous solid, used as it is, for subsequent syntheses.

PRI me R 47. Carrying out the synthesis according to a method similar to that described in example 27, but based on 1.45 g of 2-amino-N- / 3,3-dimethylpiperidinocarbonylmethyl / -N- / 2- (N -methylanilino) -carbonylphenyl / -acetamide and 0.63 g of 3-isocyanatoethylbenzoate, 1 g of 3- {3-N- (3,3-dimethylpiperidinocarbonylmethyl) -N- [2- (N-methylanilino) -carbonylphenyl] -carbonylmethyl } -ureido-ethylbenzoate, melting at 225 ^o C.

 2-amino-N- (3,3-dimethylpiperidinocarbonylmethyl / -N- / 2- (N-methylanilino) -carbonylphenyl / -acetamide can be obtained by the method similar to that described in example 27 to obtain 2- {2- amino-N- / 2- (3,3-dimethylpiperidino) -carbonylphenyl / -acetamido} tert-butyl acetate, but starting from 2.3 g of N- (3,3-dimethylpiperidinocarbonylmethyl) -N- / 2- (N- methylanilino) -carbonylphenyl / -2-phthalimidoacetamide and 0.6 g of hydrazine hydrate, yielding 1.45 g of 2-amino-N- / 3,3-dimethylpiperidinocarbonylmethyl / -N- / 2- (N-methylanilino) -carbonylphenyl / -acetamide in the form of a liquid oil used t Kim, as it is, the subsequent syntheses.

N- / 3,3-Dimethylpiperidinocarbonylmethyl / -N- / 2- (N-methylanilino) -carbonylphenyl / -2-phthalimidoacetamide can be prepared as follows. To a solution containing 6.8 g of 2- {N- / 2- (N-methylanilino) -carbonylphenyl / -2-phthalimidoacetamido} -acetic acid and 30 mg of N, N-dimethyl-4-aminopyridine in 150 cm ^{3 of} tetrahydrofuran, 2.35 g of N, N'-diimidosolcarbonyl and 1.6 g of 3,3-dimethylpiperidine are successively added at a temperature close to 20 ^° C. The mixture is stirred for 70 hours at a temperature close to 20 ^° C., then concentrated to dryness under reduced pressure (2.7 kPa) and at 50 ^° C. The residue is dissolved in 250 cm ^{3 of} dichloromethane, and the solution thus obtained is washed 2 times with 75 cm ³ 1 N. an aqueous solution of sodium hydroxide, then with 100 cm ^{3 of} water. The organic phase is dried on magnesium sulfate, filtered and concentrated to dryness under reduced pressure (2.7 kPa) and at 60 ^° C. Thus, 6.6 g of N- / 3,3-dimethylpiperidinocarbonylmethyl / -N- / 2- (N -methylanilino) -carbonylphenyl / -2-phthalimidoacetamide, melting at 180 ^o C.

2- {N- / 2- (N-methylanilino) -carbonylphenyl / -2-phthalimidoacetamido} acetic acid can be prepared as follows. A solution containing 7.9 g of 2- {N- / 2- (N-methylaniline) -carbonylphenyl / -2-phthalimidoacetamido} - tert-butyl acetate in 30 cm ^{3 of} trifluoroacetic acid is stirred at a temperature close to 20 ^o C, in for 24 hours, then poured into 50 cm ^{3 of} water. The aqueous phase is extracted 3 times with 250 cm ^{3 of} dichloromethane. The organic phases are combined, washed 2 times with 150 cm ^{3 of} water, dried on magnesium sulfate, filtered, then concentrated to dryness under reduced pressure (2.7 kPa) and at 60 ^o C. The residue is treated with 100 cm ^{3 of} petroleum ether, and insoluble the product is separated by filtration and dried under reduced pressure (15 kPa) and at 30 ^o C. Thus, 6.8 g of 2- {N- / 2- (N-methylanilino) -carbonylphenyl / -2-phthalimidoacetamido} -acetic acid are obtained in the form of an amorphous solid, used as it is, for subsequent syntheses.

PRI me R 48. Carrying out the synthesis according to the method similar to that described in example 27, but based on 1.8 g of 2- / 2-amino-N- (2-tert-butoxycarbonylphenyl) -acetamido / -tert-butyl acetate and 0.64 g of 3-methylphenyl isocyanate, 1.3 g of 2- {2- [3- (3-methylphenyl) ureido] -N- (2-tert-butoxycarbonylphenyl) -acetamido} tert-butyl acetate, melting, are obtained. at 146 ^o C.

 2- / 2-amino-N- (2-tert-butoxycarbonylphenyl) -acetamido / tert-butyl acetate can be obtained by a method similar to that described in example 27 to obtain 2- {2-amino-N- / 2 - (3,3-dimethylpiperidino) -carbonylphenyl / -acetamido} -tert-butyl acetate, but starting from 2.4 g of 2- / 2-phthalimido-N- (2-tert-butoxycarbonylphenyl) -acetamido / -tert-butyl- acetate and 0.7 g of hydrazine hydrate. In this way, 1.8 g of 2- / 2-amino-N- (2-tert-butoxycarbonylphenyl) -acetamido / -tert-butyl acetate are obtained in the form of a liquid oil, used as it is for subsequent syntheses.

2- / 2-Phthalimido-N- (2-tert-butoxycarbonylphenyl) -acetamido / tert-butyl acetate can be obtained by a method similar to that described in example 46 to obtain 2- {N- / 2- (N- methylanilino) -carbonylphenyl / -2-phthalimidoacetamido} -N-methyl-N-phenylacetamide, but starting from 3.8 g of 2- / 2-phthalimidoacetamido / -benzoate-tert-butyl, 2.15 g of tert-butyl bromoacetate and 1 5 g of potassium carbonate. Thus, 2 g of 2- / 2-phthalimido-N- (2-tert-butoxycarbonylphenyl) acetamido / tert-butyl acetate are obtained, melting at 143 ^° C.

2- / 2-Phthalimidoacetamido / -tert-butyl-benzoate can be obtained by a method similar to that described in example 27 to obtain N- / 2- (3,3-dimethylpiperidino) -carbonylphenyl / -2-phthalimidoacetamido, but starting from 3.3 g of tert-butyl anthranilate, 4.96 g of 2-phthalimidoacetyl chloride and 2.24 g of triethylamine. Thus, 5.6 g of tert-butyl 2- / 2-phthalimidoacetamido / benzoate are obtained, melting at 159 ^° C.

 Tert-butyl anthranilate can be prepared according to the method described in W.E. Gaines, N.B. Carson, J. Econ. Entomol. 39, 763 (1946).

PRI me R 49. To a solution containing 1.7 g of 2- {2 / (1-imidazolyl) -carboxamido / -N- / 3-methoxyphenyl / acetamido} -N-methyl-N-phenylacetamide in 35 cm ^{3 of} toluene, 1.1 g of 2- / 3-aminophenyl / ethanol are added. The mixture is heated at reflux for 4 hours, then concentrated to dryness under reduced pressure (2.7 kPa) and at 45 ^o C. The residue is dissolved in 60 cm ^{3 of} ethyl acetate, and the resulting solution is washed with 20 cm ³ 2 N. an aqueous solution of hydrochloric acid, then 2 times 25 cm ³ . The organic phase is dried on magnesium sulfate and concentrated to dryness under reduced pressure (2.7 kPa) and at 40 ^o C. The obtained crude product is purified by chromatography on 50 g of silica (0.065-0.205 mm) in a column with a diameter of 2.1 cm (eluent: ethyl acetate-ethanol (95: 5 by volume)), collecting fractions of 20 cm ³ . Fractions 4 to 6 are combined and concentrated to dryness under reduced pressure (2.7 kPa) and at 40 ^° C. After recrystallization in a mixture of diisopropyl ether and ethyl acetate (90:10 by volume), 0.85 g of 2- {2- [3- / 3- (2-hydroxyethyl) -phenyl / -ureido] -N- (3-methoxyphenyl) -acetamido} -N-methyl-N-phenylacetamide, melting at 90 ^o C.

2- {2- (1-Imidazolyl) -carboxamido / -N- / 3-methoxyphenyl / -acetamido} -N-methyl-N-phenylacetamide can be prepared as follows. To a solution containing 3.0 N, N'-diimidazolecarbonyl in 30 cm ^{3 of} anhydrous tetrahydrofuran, a solution containing 3.1 2- (2-amino-N- (3-methoxyphenyl) -acetamido / -N-methyl-N phenylacetamide in 30 cm ³ anhydrous tetrahydrofuran. The solution is stirred for 16 hours at a temperature close to 25 ^o C, then concentrated to dryness under reduced pressure (2.7 kPa) and at 40 ^o C. The residue is dissolved in 50 cm ^{3 of} ethyl acetate, and the resulting solution is washed successively 4 times with 30 cm ³ water and with 30 cm ^{3 of a} saturated aqueous solution of sodium chloride. The organic phase is dried on magnesium sulfate, the stream is concentrated to dryness under reduced pressure (2.7 kPa) and at 40 ^° C. After recrystallization in ethyl acetate, 3.5 g of 2- {2 - / (1-imidazolyl) -carboxamido / -N are obtained - / 3-methoxyphenyl / -acetamido} -N-methyl-N-phenylacetamide, melting at 130 ^o C.

 2- / 3-aminophenyl / ethanol can be obtained according to the method described in the article B. Sarnmalm et coll. Acta Pharm. Suedica, 11, 33, (1974).

PRI me R 50. Carry out the synthesis according to a method similar to that described in example 26, but based on 2 g of 2- {3- [3- / N- (3-methoxyphenyl) -N- (N-methyl -N-phenylcarbamylmethyl) carbamylmethyl / - ureido] phenyl} methyl propionate (RS) and 3.8 cm ³ 1 N an aqueous solution of sodium hydroxide. Thus, 1.3 g of 2- {3- / 3- / N- (3-methoxyphenyl) -N- (N-methyl-N-phenylcarbamylmethyl) -carbamylmethyl / -ureido] phenyl} propionic acid (RS) is obtained melting at 127 ^o C.

2- {3- [3-N- (3-Methoxyphenyl) -N- (N-methyl-N-phenylcarbamylmethyl) -carbamylmethyl /-ureido] phenyl} methyl propionate (RS) can be obtained by a method similar to that which is described in example 49 to obtain 2- {2- [3- / 3- (2-hydroxyethyl) phenyl / ureido] -N- / 3-methoxyphenyl / acetamido} -N-methyl-N-phenylacetamide, but starting from 2.5 g of 2- {2 - / (1-imidazolyl) -carboxamido / -N- / 3-methoxyphenyl / acetamido} -N-methyl-N-phenylacetamide and 2.1 g of 2- / 3- aminophenyl / methyl propionate (RS). The resulting crude product is purified by chromatography on 50 g of silica (0.065-0.200 mm) in a column with a diameter of 2.5 cm (eluent: methylene chloride-ethyl acetate (60:40 by volume)), collecting fractions of 50 cm ³ . Fractions 5 to 12 are combined and concentrated to dryness under reduced pressure (2.7 kPa) and at 40 ^° C. 2.1 g of 2- {3- [3-N- (3-methoxyphenyl) -N- (thus obtained) are thus obtained. N-methyl-N-phenylcarbamylmethyl / -ureido] phenyl} methyl propionate (RS) in the form of a substance such as "meringue", used as it is, for subsequent syntheses.

2- (3-aminophenyl) methyl propionate (RS) can be prepared as follows. To a solution containing 4 g of 2- (3-nitrophenyl) methyl propionate (RS) in 50 cm ^{3 of} ethanol is added 0.3 g of palladium supported on activated carbon with a content of 5%. The suspension is stirred for 2 hours at a temperature close to to 25 ^o C, in a hydrogen atmosphere (100 kPa). Then the catalyst is separated by filtration, and the filtrate is concentrated to dryness under reduced pressure (2.7 kPa) and at 40 ^° C. 3.3 g of 2- / 3-aminophenyl / methyl propionate (RS) are thus obtained in the form of a liquid oil, used as it is for subsequent syntheses.

2- (3-Nitrophenyl) methyl propionate (RS) can be prepared as follows. Gaseous hydrochloric acid was bubbled for 3 hours through a solution containing 5 g of 2- / 3-nitrophenyl / propionitrile- (RS) in 40 cm ^{3 of} methanol. The resulting mixture was stirred at reflux for 30 minutes, then the insoluble product was separated by filtration. The filtrate is concentrated to dryness under reduced pressure (2.7 kPa) and at 40 ^o C. The crude product is purified by chromatography on 80 g of silica (0.065-0,200 mm) in a column with a diameter of 3.5 cm (eluent: petroleum ether-ethyl acetate (80:20 by volume)), collecting fractions of 100 cm ³ . Fractions 1 and 2 are combined and concentrated to dryness under reduced pressure (2.7 kPa) and at 40 ^° C. 4.0 g of 2- / 3-nitrophenyl / methyl propionate (RS) are also thus obtained in the form of a liquid oil used as it is, for subsequent syntheses.

 2- / 3-Nitrophenyl / -propionitrile- (RS) can be obtained by the method described in the article by E. Felder et coll. J. Med. Chem. 13, 559, (1970).

PRI me R 51. The synthesis is carried out according to a method similar to that described in example 49, but starting from 1.7 g of 2- {2 - / (1-imidazolyl) -carboxiamido / -N- / 3-methoxyphenyl / -acetamido} -N-methyl-N-phenylacetamide and 1.4 g of 5- / 3-aminobenzyl / -tetrazole. The resulting crude product is purified by chromatography on 40 g of silica (0.065-0.200 mm) in a column with a diameter of 2 cm (eluent: methylene chloride-ethanol (90:10 by volume)), collecting fractions of 25 cm ³ . Fractions 5 to 123 are combined and concentrated to dryness under reduced pressure (2.7 kPa) and at 40 ^° C. After recrystallization in ethyl acetate-diisopropyl ether (10:90 by volume), 0.2 g of 2- {N - / 3-methoxyphenyl / -2- {3- [3 - / (5-tetrazolyl) methyl / phenyl] ureido} -acetamido} -N-methyl-N-phenylacetamide, melting at 120 ^o C.

5- / 3-Aminobenzyl / -tetrazole can be prepared as follows. To a solution containing 3.9 g of 5- / 3-nitrobenzyl / tetrazole in 80 cm ^{3 of} ethanol is added 0.3 g of palladium supported on activated carbon with a content of 5%. The suspension is stirred for 2 hours at a temperature close to 25 ^o C, in a hydrogen atmosphere (100 kPa). The catalyst was separated by filtration, and the filtrate was concentrated to dryness under reduced pressure (2.7 kPa) and at 40 ^° C. 3.1 g of 5- / 3-aminobenzyl / -tetrazole melting at 140 ^° C were thus obtained.

5- / 3-Nitrobenzyl / -tetrazole can be prepared as follows. To a solution containing 1.6 g of 3-nitrophenylacetonitrile in 25 cm ^{3 of} anhydrous dimethylformamide, 1.43 g of sodium azide and 1.17 g of anhydrous ammonium chloride are added. The mixture is stirred at a temperature close to 100 ^° C. for 22 hours, then concentrated to dryness under reduced pressure (1.2 kPa) and at 80 ^° C. The resulting residue is taken up in 25 cm ³ 2N. a solution of hydrochloric acid, and the resulting mixture is extracted 2 times with 50 cm ^{3 of} methylene chloride. The combined organic phases are dried on magnesium sulfate and concentrated to dryness under reduced pressure (2.7 kPa) and at 35 ^o C. Thus, 1.6 g of 5- / 3-nitrobenzyl / -tetrazole melting at 140 ^o C.

3-Nitrophenylacetonitrile can be prepared as follows. To a solution containing 20.6 g of 3-nitrobenzyl chloride in 120 cm ^{3 of} methanol, 20 cm ^{3 of an} 8.5 M aqueous solution of potassium cyanide are added. The mixture is stirred at reflux for 4 hours, then concentrated to dryness under reduced pressure (2.7 kPa) and at 45 ^° C. The residue is taken up in 200 cm ^{3 of} diethyl ether and 150 cm ^{3 of} water. The organic phase is dried on magnesium sulfate and concentrated to dryness under reduced pressure (2.7 kPa) and at 35 ^o C. The obtained crude product is purified by chromatography on 50 g of silica (0.065-0,200 mm) in a column with a diameter of 2 cm (eluent : methylene chloride), collecting fractions of 30 cm ³ . Fractions 4 to 9 are combined and concentrated under reduced pressure (2.7 kPa) and at 40 ^° C. 11 g of 3-nitrophenylacetonitrile are thus obtained, melting at 60 ^° C.

PRI me R 52. The synthesis is carried out by a method similar to that described in example 49, but based on 1.0 g of 2- {2 - / (1-imidazolyl) -carboxamido / -N- / 3-hydroxyphenyl / -acetamido} -N-methyl-N-phenylacetamide and 0.6 g of 3-aminophenylmethanol. The crude product is purified by chromatography on 40 g of silica (0.065-0.200 mm) in a column with a diameter of 2 cm (eluent: ethano-ethyl acetate (5: 95 by volume)), collecting fractions of 10 cm ³ . Fractions 7 to 13 are combined and concentrated to dryness under reduced pressure (2.7 kPa) and at 40 ^° C. After recrystallization in ethyl acetate-diisopropyl ether (80:20 by volume), 0.2 g of 2- {2- / 3- (3-hydroxymethylphenyl) -ureido / -N- / 3-hydroxyphenyl / -acetamido} -N-methyl-N-phenylacetamide, melting at 160 ^o C.

 2- {2 - / (1-Imidazolyl) -carboxamido / -N- / 3-hydroxyphenyl / -acetamido} -N-methyl-N-phenylacetamide can be obtained by a method similar to that described in example 49 to obtain 2 - {2 - / (1-imidazolyl) -carboxamido / -N- / 3-methoxyphenyl / -acetamido} -N-methyl-N-phenylacetamide, but starting from 0.9 g of 2-amino-N- (3-hydroxyphenyl ) -acetamido / -N-methyl-N-phenylacetamide and 0.7 g of N, N'-diimidazolecarbonyl. Thus, 0.9 g of 2- {2 - / (1-imidazolyl) -carboxamido / -N- / 3-hydroxyphenyl / -acetamido} -N-methyl-N-phenylacetamide is obtained in the form of a liquid oil, such as that used there is, for subsequent syntheses.

 2- / 2-amino-N- / 3-hydroxyphenyl / -acetamido / -N-methyl-N-phenylacetamide can be obtained by a method similar to that described in example 4 to obtain 2- / 2-amino-N- (2-trifluoromethoxyphenyl) -acetamido / tert-butyl acetate, but starting from 2.0 g of 2- / N- (3-hydroxyphenyl) -2-phthalimidoacetamido / -N-methyl-N-phenylacetamide and 0.45 g of hydrate hydrazine. Thus, 0.9 g of 2- / 2-amino-N- (3-hydroxyphenyl) -acetamido / -N-methyl-N-phenylacetamide is obtained in the form of a liquid oil, used as it is for subsequent syntheses.

2- / N- (3-Hydroxyphenyl) -2-phthalimidoacetamido / -N-methyl-N-phenylacetamide can be prepared as follows. A solution containing 13 g of 2- / N- (3-methoxyphenyl) -2- is added in 10 min to a 1 M solution of 13.3 cm ³ boron tribromide in methylene chloride, which is maintained in a nitrogen atmosphere and at a temperature close to -50 ^° C. phthalimidoacetamido / -N-methyl-N-phenylacetamide in 20 cm ^{3 of} methylene chloride. The resulting mixture is stirred for 30 minutes at a temperature close to -50 ^o C, then 16 hours at a temperature close to 20 ^o C. Then add 25 cm ³ water, then 25 cm ³ methylene chloride. The organic phase is separated by decantation, washed 4 times with 30 cm ^{3 of} water, dried on magnesium sulfate and concentrated to dryness under reduced pressure (2.7 kPa) and at 40 ^o C. Thus, 0.9 g of 2- / N- ( 3-hydroxyphenyl) -2-phthalimidoacetamido / -N-methyl-N-phenylacetamide as a liquid oil, used as such for subsequent syntheses.

PRI me R 53. Carry out the synthesis according to a method similar to that described in example 1, but based on 1.0 g of 2- / 2-amino-N- (2-ethoxyphenyl) -acetamido / -N-methyl -N-phenylacetamide and 0.33 g of 3-methylphenyl isocyanate. The resulting crude product is purified by chromatography on 40 g of silica (0.065-0.200 mm) in a column with a diameter of 2.0 cm (eluent: cyclohexane-ethyl acetate (30:70 by volume)), collecting fractions of 20 cm ³ . Fractions 5 to 13 are combined and concentrated to dryness under reduced pressure (2.7 kPa) and at 40 ^o C. After recrystallization in a mixture of ethyl acetate-diisopropyl ether (10: 90 by volume), 0.3 g of 2- {N- / 3-ethoxyphenyl / -2- / 3- (3-methylphenyl) -ureido / -acetamido} -N-methyl-N-phenylacetamide, melting at 98 ^o C.

 2- / 2-amino-N- (3-ethoxyphenyl) -acetamido / -N-methyl-N-phenylacetamide can be obtained by a method similar to that described in example 4 to obtain 2- / 2-amino-N- (2-trifluoromethoxyphenyl) -acetamido / -tert-butyl acetate, but starting from 1.2 g of 2- / N- (3-ethoxyphenyl) -2-phthalimidoacetamido / -N-methyl-N-phenylacetamide and 0.28 g of hydrazine hydrate . Thus, 1 g of 2- / 2-amino-N- (3-ethoxyphenyl) -acetamido / -N-methyl-N-phenylacetamide is obtained in the form of a liquid oil, used as it is for subsequent syntheses.

2- / N- (3-Ethoxyphenyl) -2-phthalimidoacetamido / -N-methyl-N-phenylacetamide can be prepared as follows. To a solution containing 2.7 g of 2- / N- (3-hydroxyphenyl) -2-phthalimidoacetamido / -N-methyl-N-phenylacetamide in 15 cm ^{3 of} N, N-dimethylformamide is added at a temperature close to 10 ^o C 0.24 g of an oil suspension of sodium hydride (50 wt.). The suspension is stirred for 30 minutes at a temperature close to 10 ^° C., then 1.0 g of ethyl iodide is added. The mixture is stirred for 2 hours at a temperature close to 25 ^o C, then poured into a mixture consisting of 150 cm ^{3 of} water and 200 cm ^{3 of} ethyl acetate. The organic phase is separated by decantation, washed with 2 times 100 cm ^{3 of} water, dried on magnesium sulfate and concentrated to dryness under reduced pressure (2.7 kPa) and at 35 ^o C. The crude product is purified by chromatography on 50 g of silica (0.063-0 , 2 mm), located in a column with a diameter of 2.5 cm (eluent: cyclohexane-ethyl acetate (40: 60 by volume)), collecting fractions of 20 cm ³ . Fractions 4 to 7 are combined and concentrated to dryness under reduced pressure (2.7 kPa) and at 40 ^° C. 1.2 g of 2- / N- (3-ethoxyphenyl) -2-phthalimidoacetamido / -N-methyl are thus obtained -N-phenylacetamide in the form of a liquid oil, used as it is, for subsequent syntheses.

PRI me R 54. The synthesis is carried out by a method similar to that described in example 1, but based on 0.8 g of 2- / 2-amino-N- (3-methoxyphenyl) -acetamido / -N- / 2-fluorophenyl / -N-methylacetamide and 0.32 g of 3-methylphenyl isocyanate. The resulting product is purified by chromatography on 40 g of silica (0.065-0.200 mm) in a column with a diameter of 2 cm (eluent: methylene chloride-ethanol (95: 5 by volume)), collecting fractions of 20 cm ³ . Fractions 8 to 12 are combined and concentrated to dryness under reduced pressure (2.7 kPa) and at 40 ^o C. After recrystallization in a mixture of diisopropyl ether-acetonitrile (90: 10 by volume), 0.7 g of N- / 2-fluorophenyl / -2- {N- / 3-methoxyphenyl / -2- / 3- (3-methylphenyl) -ureido / -acetamido} -N-methylacetamide, melting at 110 ^o C.

 2- / 2-amino-N- (3-methoxyphenyl) -acetamido / -N- / 2-fluorophenyl / -N-methylacetamide can be obtained by a method similar to that described in example 4 to obtain 2- / 2- amino-N- (2-trifluoromethoxyphenyl) -acetamido / -acetate tert-butyl, but starting from 6.2 g of N- / 2-fluorophenyl / -2- / N- (3-methoxyphenyl) -2-phthalimidoacetamido / -N -methylacetamide and 1.3 g of hydrazine hydrate. Thus, 4.0 g of 2- / 2-amino-N- (3-methoxyphenyl) -acetamido / -N- / 2-fluorophenyl / -N-methylacetamide is obtained in the form of a liquid oil, used as it is, for the subsequent syntheses.

N- / 2-Fluorophenyl / -2- / N- (3-methoxyphenyl-2-phthalimidoacetamido / -N-methylacetamide can be prepared as follows: To a suspension containing 9.2 g of 2- (N- (3-methoxyphenyl) -2-phthalimidoacetamido / -acetic acid in 150 cm ^{3 of} 1,2-dichloroethane, 3.5 g of oxalyl dichloride, then 0.2 cm ^{3 of} dimethylformamide are added, the mixture is stirred for 2 hours at a temperature close to 25 ^o C, then added 3.1 g of 2-fluoro-N-methylaniline and 2 g of pyridine dissolved in 20 cm ^{3 of} 1,2-dichloroethane.The solution is stirred for 2 hours at a temperature close to 25 ^o C, then washed 2 times with 100 cm ³ water. The organic phase is dried on magnesium sulfate and concentrated to dryness under reduced pressure (2.7 kPa) and at 40 ^o C. The obtained crude product is purified by chromatography on 80 g of silica (0.065-0,200 mm) in a column with a diameter of 4.0 cm (eluent: methylene chloride-methanol (98: 2 by volume)), collecting fractions of 30 cm ^3. Fractions 5 to 13 are combined and concentrated to dryness under reduced pressure (2.7 kPa) and at 40 ^o C. Thus, 6 , 2 g of N- / 2-fluorophenyl / -2- / N- (3-methoxyphenyl) -2-phthalimidoacetamido / -N-methylacetamide as a meringue type substance used as it is, for subsequent syntheses.

2- / N- (3-Methoxyphenyl) -2-phthalimidoacetamido / acetic acid can be prepared as follows. To a solution containing 19 g of 2- / N- (3-methoxyphenyl) -2-phthalimidoacetamido / t-butyl acetate in 220 cm ^{3 of} dichloromethane, 32.9 g of trifluoroacetic acid was added. The resulting solution was stirred at reflux for 4 hours, then concentrated to dryness under reduced pressure (2.7 kPa) and at 40 ^° C. After recrystallization in diisopropyl ether, 16 g of 2- / N- (3-methoxyphenyl) -2 were obtained -phthalimidoacetamido / -acetic acid, melting at 198 ^o C.

2-Fluoro-N-methylaniline can be prepared as follows. To a suspension containing 4.9 g of lithium aluminum hydride in 100 cm ^{3 of} anhydrous tetrahydrofuran, kept at a temperature close to 25 ^o C, a solution containing 12.2 g of 2-fluoroformanilide in 100 cm ^{3 of} anhydrous tetrahydrofuran is added over 15 minutes. The mixture is stirred at a temperature close to 25 ^o C for 3 hours. After cooling to a temperature close to 5 ^o C, sequentially are added: 5.7 cm ^{3 of} water, 4.2 cm ³ 5 N. an aqueous solution of sodium hydroxide, then 19 cm ^{3 of} water. The resulting suspension is stirred for 30 minutes, then 150 cm ^{3 of} diethyl ether are added. The insoluble product is separated by filtration, and the filtrate is concentrated to dryness under reduced pressure (2.7 kPa) and at 40 ^° C. The residue is dissolved in 60 cm ^{3 of} dichloromethane and the solution is dried on magnesium sulfate, then concentrated to dryness under reduced pressure (2.7 kPa) ) and at 40 ^° C. 7.2 g of 2-fluoro-N-methylaniline are thus obtained in the form of a liquid oil, used as it is for subsequent syntheses.

2-Fluoroformanilinide can be prepared as follows. To a solution containing 10.8 g of sodium methylate in 100 cm ^{3 of} anhydrous dimethylformamide, 11 g of 2-fluoroaniline was added. The mixture is heated at reflux for 2 hours, distilling off the methanol formed, then concentrated to dryness under reduced pressure (0.01 kPa) and at 60 ^° C. The residue is taken up in 1 liter of water and 300 cm ^{3 of} diethyl ether. The organic phase is separated by decantation, dried on magnesium sulfate and concentrated to dryness under reduced pressure (2.7 kPa) and at 30 ^o C. 12.2 g of 2-fluoroformanilide are thus obtained in the form of a liquid oil, used as it is, for subsequent syntheses.

PRI me R 55. The synthesis is carried out by a method similar to that described in example 26, but based on 3.1 g of 3- {3- [N- / 2- (3,4-dihydro-1,4 -2H-benzothiazin-4-yl) -2-hydroxyethyl / -N- / 3-methoxyphenyl / carbamylmethyl] ureido} ethyl benzoate and 5.5 cm ³ 1 N an aqueous solution of sodium hydroxide. Thus, 1.6 g of 3- {3- [N- / 2- (3,4-dihydro-1,4-2H-benzothiazin-4-yl) -2-oxoethyl / -N-3-methoxyphenyl / - carbamylmethyl] -ureido} -benzoic acid, melting at 165 ^o C.

3- {3- [N- / 2- (3,4-dihydro-1,4-2H-benzothiazin-4-yl) -2-hydroxyethyl / -N- / 3-methoxyphenyl / carbamylmethyl] ureido} - ethylbenzoate can be obtained by a method similar to that described in example 49 to obtain 2- {2- [3- / 3- (2-hydroxyethyl) phenyl / ureido] -N- / 3-methoxyphenyl / acetamido} -N-methyl-N-phenylacetamide, but starting from 3.0 g of N- / 2- (3,4-dihydro-1,4-2H-benzothiazin-4-yl) -2-hydroxyethyl / -2 - / ( 1-imidazolyl) -carboxamido / -N- / 3-methoxyphenyl / -acetamide and 2.2 g of ethyl 3-aminobenzoate. The resulting product is purified by chromatography on 150 g of silica (0.065-0,200 m) located in a column with a diameter of 5 cm (eluent: methylene chloride-ethyl acetate (70:30 by volume)), collecting fractions of 30 cm ³ . Fractions 24 to 36 are combined and concentrated to dryness under reduced pressure (2.7 kPa) and at 40 ^° C. 3.2 g of 3- {3- [N- / 2- (3,4-dihydro-1) are thus obtained. , 4-2H-benzothiazin-4-yl) -2-oxoethyl / -N- / 3-methoxyphenyl / carbamylmethyl] -ureido} ethylbenzoate in the form of a substance such as "meringue", used as it is, for subsequent syntheses .

 N- / 2- (3,4-dihydro-1,4-2H-benzothiazin-4-yl) -2-oxoethyl / -2 - / (1-imidazolyl) carboxamido / -N- / 3-methoxyphenyl / - acetamide can be obtained by a method similar to that described in example 49 to obtain 2- {2 - / (1-imidazolyl) -carboxamido / -N- / 3-methoxyphenyl / -acetamido} -N-methyl-N-phenylacetamide but based on 3.6 g of 2-amino-N- / 2- (3,4-dihydro-1,4-2H-benzothiazin-4-yl) -2-oxoethyl / -N- / 3-methoxyphenyl / - acetamide and 2.6 g of N, N'-diimidazolecarbonyl. Thus, 3.1 g of N- / 2- (3,4-dihydro-1,4-2H-benzothiazin-4-yl) -2-oxoethyl / -2 - / (1-imidazolyl) -carboxamido / -N are obtained - / 3-methoxyphenyl / -acetamide in the form of an amorphous powder, used as it is, for subsequent syntheses.

 2-amino-N- / 2- (3,4-dihydro-1,4-2H-benzothiazin-4-yl) -2-oxoethyl / -N- / 3-methoxyphenyl / -acetamide can be obtained by a method similar to to that described in example 4 to obtain 2- / 2-amino-N- (2-trifluoromethoxyphenyl) -acetamido / -acetate tert-butyl, but starting from 8.0 g of N- / 2- (3,4-dihydro -1.4-2H-benzothiazin-4-yl) -2-oxoethyl / -N- / 3-methoxyphenyl / -2-phthalimidoacetamide and 1.6 g of hydrazine hydrate. Thus, 5.9 g of 2-amino-N- / 2- (3,4-dihydro-1,4-2H-benzothiazin-4-yl) -2-oxoethyl / -N- / 3-methoxyphenyl-acetamide are obtained in as a liquid oil, used as it is, for subsequent syntheses.

N- / 2- (3,4-Dihydro-1,4-2H-benzothiazin-4-yl) -2-oxoethyl / -N- / 3-methoxyphenyl / -2-phthalimidoacetamide can be prepared by a method similar to that which is described in example 54 to obtain N- / 2-fluorophenyl / -2- / N- (3-methoxyphenyl) -2-phthalimidoacetamido / -N-methyl-acetamide, but based on 9.2 g of 2- / N- ( 3-methoxyphenyl) -2-phthalimidoacetamido / acetic acid, 3.5 g of oxalyl dichloride, 3.8 g of 3,4-dihydro-1,4-2H-benzothiazine and 2 g of pyridine. Recrystallization in a mixture of acetonitrile-diisopropyl ether (35:65 by volume) gives 8.2 g of N- / 2- (3,4-dihydro-1,4-2H-benzothiazin-4-yl) -2-oxoethyl / - N- / 3-methoxyphenyl / -2-phthalimidoacetamide, melting at 150 ^o C.

 3,4-Dihydro-1,4-2H-benzothiazine can be obtained by the method described in the article by C.C.J. Culvenor et coll. J. Chem. Soc. 278 (1949).

PRI me R 56. The synthesis is carried out by a method similar to that described in example 26, but based on 0.7 g of 3- {3- / N- / 3-methoxyphenyl / -N- / 2- (1 , 2,3,4-tetrahydro-1-quinolyl) -2-oxoethyl / carbamylmethyl] -ureido} ethylbenzoate and 1.3 cm ³ 1 N an aqueous solution of sodium hydroxide. Thus, 0.2 g of 3- {3- [N- / 3-methoxyphenyl-N- / 2- (1,2,3,4-tetrahydro-1-quinolyl) -2-oxoethyl / - carbamylmethyl] -ureido is obtained } -benzoic acid, melting at 190 ^o C.

Ethyl 3- {3- [N- / 3-methoxyphenyl / -N- / 2- (1,2,3,4-tetrahydro-1-quinolyl) -2-oxoethyl / carbamylmethyl] -ureido} ethyl benzoate may be obtained by a method similar to that described in example 49 to obtain 2- {2- [3- / 3- (2-hydroxyethyl) phenyl / ureido] -N- / 3-methoxyphenyl / acetamido} -N- methyl N-phenylacetamide, but starting from 1.2 g of 2 - / (1-imidazolyl) -carboxamido / -N- / 3-methoxyphenyl / -N- / 2- (1,2,3,4-tetrahydro-1 -quinolyl) -2-oxoethyl / -acetamide and 0.85 g of ethyl 3-aminobenzoate. The resulting product is purified by chromatography on 40 g of silica (0.065-0,200 mm) in a column with a diameter of 2 cm (eluent: methylene chloride-ethyl acetate (70:30 by volume)), collecting fractions of 20 cm ³ . Fractions 31 to 40 are combined and concentrated to dryness under reduced pressure (2.4 kPa) and at 40 ^° C. Thus, 0.7 g of 3- {3- [N- / 3-methoxyphenyl / -N- / 2- (1,2,3,4-tetrahydro-1-quinolyl) -2-oxoethyl / carbamylmethyl] ureido} ethylbenzoate in the form of a substance such as "meringue", used as it is, for subsequent syntheses.

 2 - / (1-Imidazolyl) -carboxamido / -N- / 3-methoxyphenyl / -N- / 2- (1,2,3,4-tetrahydro-1-quinolyl) -2-oxoethyl / -acetamide can be obtained according to a method similar to that described in example 49 to obtain 2- {2 - / (1-imidazolyl) -carboxamido / -N- / 3-methoxyphenyl / acetamido} -N-methyl-N-phenylacetamide, but based on 5.0 g of 2-amino-N- / 3-methoxyphenyl / -N- / 2- (1,2,3,4-tetrahydro-1-quinolyl) -2-oxoethyl / acetamide and 4.2 g of N, N'-diimidazolecarbonyl. Thus, 2.3 g of 2 - / (1-imidazolyl) -carboxamido / -N- / 3-methoxyphenyl / -N- / 2- (1,2,3,4-tetrahydro-1-quinolyl) -2- are obtained oxoethyl / -acetamide in the form of a substance such as "meringue", used as it is, for subsequent syntheses.

 2-amino-N- / 3-methoxyphenyl / -N- / 2- (1,2,3,4-tetrahydro-1-quinolyl) -2-oxoethyl / -acetamide can be obtained by a method similar to that described in example 4 to obtain 2- / 2-amino-N- (2-trifluoromethoxyphenyl) -acetamido / tert-butyl acetate, but starting from 8.5 g of N- / 3-methoxyphenyl / -2-phthalimido-N- / 2 - (1,2,3,4-tetrahydro-1-quinolyl) -2-oxoethyl / acetamide and 1.7 g of hydrazine hydrate. Thus, 5 g of 2-amino-N- / 3-methoxyphenyl / -N- / 2- (1,2,3,4-tetrahydro-1-quinolyl) -2-oxoethyl / acetamide are obtained in the form of a liquid oil used as it is, for subsequent syntheses.

 N- / 3-Methoxyphenyl / -2-phthalimido-N- / 2- (1,2,3,4-tetrahydro-1-quinolyl) -2-oxoethyl / acetamide can be obtained by a method similar to that described in example 54 to obtain N- / 2-fluorophenyl / -2- / N- (3-methoxyphenyl) -2-phthalimido-acetamido / -N-methylacetamide, but based on 8.0 g of 2- / N- (3- methoxyphenyl) -2-phthalimidoacetamido / acetic acid, 3.0 g of oxalyl chloride, 3.5 g of 1,2,3,4-tetrahydroquinoline and 1.8 g of pyridine. Thus, 8.8 g of N- / 3-methoxyphenyl / -2-phthalimido-N- / 2- (1,2,3,4-tetrahydro-1-quinolyl) -2-oxoethyl / acetamide are obtained in the form of a liquid oil used as it is for subsequent syntheses.

Working in a similar way, but using the appropriate source, the following compounds are obtained:
A) +2 (S) - {3- {3 - {[N- (3-methoxyphenyl) -N-1- (N-methyl-N-phenylcarbamyl) - (R, S) ethyl] -carbamylmethyl} - ureido} phenyl} propionic acid, melting at 151 ^o C;
B) 2-fluoro-5- {3- [N- (3-methoxyphenyl) -N- (N-methyl-N-phenylcarbamylmethyl) -carbamylmethyl] -ureido} benzoic acid, melting at 140 ^° C;
C) potassium salt of 3- {3- [N- (3-methoxyphenyl) -N- / N-methyl-N-phenylcarbamylmethyl) carbamylmethyl)] ureido} phenyl} methanesulfonic acid, melting at 180 ^° C;
D) a potassium salt of 1- {3- {3- [N- (3-methoxyphenyl) -N- (N-methyl-N-phenylcarbamylmethyl) carbamylmethyl] ureido} phenyl} ethanesulfonic acid, melting at 190 ^° C;
E) methyl 2- {3- {3- [N- (3-methoxyphenyl) -N- (N-methyl-N-phenylcarbamylmethyl) -carbamylmethyl] -ureido} phenyl} propionate, melting at 160 ^° C;
F) / E / -2- {2- {3- [3- (1-hydroxyiminoethyl) phenyl] -ureido} -N- (3-methoxyphenyl) acetamido} -N-methyl-N-phenylacetamide, melting at 188 ^o C;
G) 3- {3- [N- (3-methoxyphenyl) -N- (N-methyl-N-phenylcarbamylmethyl) -carbamylmethyl] -ureido} phenoxyacetic acid, melting at 118 ^° C;
H) 3 / E / - {3- [N- (3-methoxyphenyl) -N- (N-methyl-N-phenylcarbamylmethyl) -carbamylmethyl] -ureido} cinnamic acid, melting at 128 ^° C;
I) 2 / S / - {3- {3- {N-tert-butoxycarbonylmethyl-N - {[2- (3,4-dihydro-2H-benzoxazine-1,4-li-4) carbonyl] phenyl} carbamylmethyl } ureido} phenyl} -propionic acid, melting at 135-140 ^o C;
J) 2 / S / - {3- {3 - {[N- (2-morpholinocarbonylphenyl) -N-tert-butoxycarbonylmethyl] carbamylmethyl} ureido} phenyl} propionic acid, melting at 135 ^o C.

 The activity and toxicity of the examples are given in table. one.

 The invention also relates to medicines consisting of at least one compound with the formula (I) in pure form or in the form of a composition in which it is associated with any other pharmaceutically compatible product, the latter may be inert or physiologically active. The medicaments of the invention can be administered orally, parenterally, rectally or topically.

 As solid compositions for oral administration, tablets, pills, powders (gelatin capsules, cachets) or granules can be used. In these compositions, the active ingredient of the invention is mixed with one or more inert diluents such as starch, cellulose, sucrose, lactose or silica. These compositions may also contain substances other than diluents, for example, one or more lubricants such as magnesium stearate or talc, a dye, a protective coating (dragee) or a varnish coating.

 As liquid compositions for oral administration, pharmaceutically acceptable solutions, suspensions, emulsions, syrups and elixirs containing inert diluents such as water, ethanol, glycerin, vegetable liquid oils or paraffin oil can be used. These compositions may contain substances other than diluents, for example wetting, sweetening, thickening, flavoring or stabilizing compounds.

 Sterile compositions for parenteral administration may preferably be aqueous solutions or non-aqueous solutions, suspensions or emulsions. As a solvent or carrier, water, propylene glycol, polyethylene glycol, vegetable liquid oils, in particular olive oil, injectable organic esters, for example ethyl oleate, or other suitable organic solvents can be used. These compositions may also contain additives, in particular wetting, isotonizing, emulsifying, dispersing and stabilizing agents. Sterilization can be carried out in various ways, for example, by aspetizing filtration, by introducing sterilizing agents into the composition, as a result of irradiation or by heating. They can also be prepared in the form of solid sterile compositions which can dissolve upon application in a sterile, suitable or injectable medium.

 Compositions for rectal administration are suppositories or rectal capsules which contain, in addition to the active compound, indifferent substances such as cocoa butter, semi-synthetic glycerides or polyethylene glycols.

 Compositions for topical administration may be, for example, creams, ointments, lotions, eye drops, funds for the mucous membrane of the throat and mouth, drops for the nose or aerosols.

 In therapeutic practice for humans, the compounds of the invention are particularly useful in the treatment and prevention of disorders associated with CCK and gastrin at the level of the nervous system and gastrointestinal apparatus. Therefore, these compounds can be used to treat and prevent psychosis, anxiety disorders, Parkinson's disease, delayed dyskinesia, irritable bowel syndrome, acute pancreatitis, ulcers, intestinal obstruction, some tumors of the lower esophagus, colon and intestines, and in as a potentiator of the analgesic activity of narcotic and non-narcotic pain medications, as well as appetite regulators.

 Dosages depend on the desired effect, on the duration of treatment and on the route of administration: they are usually from 0.5 to 1.0 g per day by oral route for an adult with single doses ranging from 10 to 500 mg of active substance.

 In general, the attending physician will determine the appropriate dosage depending on age, weight and all other factors specific to the patient to be treated.

 The following examples illustrate the compositions of the invention.

PRI me R A. In accordance with the usual method prepare gelatin capsules with a 50 mg dosage of the compound having the following composition, mg:
3- {3- / N- (3-Methoxyphenyl) -N- (N-methyl-N-phenylcarbamylmethyl) -carbamylmethyl / - ureido} benzoic acid 50
Cellulose 18
Lactose 55
Colloidal Silica 1
Sodium Carboxymethyl Starch 10
Talc 10
Magnesium Stearate 1
PRI me R B. In accordance with the usual method, tablets are prepared with a 50 mg dosage of the active compound, having the following composition, mg:
2- {(N- / 2- (3,3-Dimethylpiperidino) -carbonylphenyl / -2- / 3- (3-methylphenyl) ureido / -acetamido} tert-butyl acetate 50
Lactose 104
Cellulose 40
Periston 10
Sodium Carboxymethyl Starch 22
Talc 10
Magnesium Stearate 2
Colloidal Silica 2
A mixture consisting of hydroxymethyl cellulose, glycerol and titanium oxide (72.0: 3.5: 24.5), in an amount bringing the weight of one final tablet coated with a thin protective layer to 245
PRI me R C. Prepare a solution suitable for injection containing 10-mg active compound, which has the following composition, mg:
3- {3- / N- (3-methoxyphenyl) -N- (N-methyl-N-phenylcarbamylmethyl) -carbamylmethyl / -ureido} phenylacetic acid 10
Benzoic acid 80
Benzyl alcohol 0.06 cm ³
Sodium Benzoate 80
95% ethanol 0.4 cm ³
Sodium hydroxide 24
Propylene glycol 1.6 cm ³
Water in an amount sufficient to bring the volume to 4 cm ³
BIOLOGICAL TESTS
Materials and methods
M aterialy. Male Swiss-Webster mice (25-35 g) were kept at 24 ^° C. for 12 h light and dark cycles (9 h 21 h), fed a Purina chon diet for rats and provided plenty of drinking water. Pure natural pork cholecystokinin (CCK ₃₃ ) was obtained from the laboratory of gastrointestinal hormones, Karolinsk Institute, Stockholm, Sweden. Synthetic CCK ₈ and desulfated CCK ₈ (dCCC ₈ ) were obtained from the Sguibb Medical Research Institute, Princeton, New Jersey. The sodium salt of N ² , O ² -dibutyryl-guanosine-3,5-cyclic monophosphoric acid (dibutyryl-cyclic GMP), the sodium salt of N ⁶ , O ² -dibutyryl-adenosine-3,5-monophosphoric acid (dibutyryl-cyclic AMP) , cyclic GMF, 4- (2-hydroxyethyl) -1-piperazine-ethanesulfonic acid (HEPES), succinic acid, Tris, bovine serum albumin type V (BSA), and ECTUC were purchased from Sigma Chemical Co. St. Louis, Missouri. Synthetic Tri-Met-Asp-Phenamide (CCK ₄ ) was purchased from Research Plus Denville, New Jersey. N-succinimidyl-3- (4-hydroxy-5- ¹²⁵ 1 iodophenyl) propionate ⁽¹²⁵ reagent 1-WH) acquired from the firm Amercham Arlington Heights, Illinois. CCK _{33 was} iodinated to a specific activity of 200-300 μCi / μg by conjugation with ¹²⁵ 1-BH reagent, as described in detail by SanKarah et al. 1979. Labeled CCK ₃₃ is referred to below as ¹²⁵ 1-BH-CCK.

P r igotovlenie to and. Mice were decapitated between 9 hours 30 minutes and 11 hours. The whole brain was removed and placed in 0.9% NaCl at 4 ^° C. The cortex was dissected in ice and homogenized in 10 volumes of 50 mM Tris buffer (pH 7.4 ) at 4 ^o C using a homogenizer with glass cups coated with Teflon and seven knives at 1600 rpm. This homogenate was centrifuged at 42,000 ^° C for 15 min at 4 ^° C. The pellet was then resuspended in the same volume of the above Tris buffer and re-centrifuged under the same conditions. The precipitate was suspended in 1 ml of incubation medium, the protein concentration in the membrane suspension was determined by the Lowry method (Lowry et al. 1951), and then it was adjusted to 0.58 mg / ml.

 Pancreatic particles were prepared in a similar manner. The whole pancreas was removed and homogenized under the same conditions that were used for the brain.

S vyzyanie ¹²⁵ -VN-KHKK. The composition of the incubation medium, which was used in experiments to study the binding of ^125- BH-CCK, was as follows: 118.0 mm NaCl; 4.7 mM KCl; 5.0 mM MgCl ₂ ; 1.0 mM EGTUK; 10.0 mm HEPES; 5.0 mg / ml BSA and 0.25 mg / ml bacitracin. When pH values between 5 and 6 were studied, succinic acid was used instead of HEPES. Other changes in the composition of the incubation medium are noted in the text.

In most experiments, freshly prepared membranes (105 mg protein) were incubated in plastic microcentrifuge tubes in 300 μl of incubation medium with 50 pM ¹²⁵ 1-BH-CCK at 24 ^° C. 1 mM CCK _{8 was} added to determine non-specific binding. Each study was performed in triplicate. At certain time intervals (typically 120 minutes), the tubes were centrifuged for 10,000 q on a Beckman microcentrifuge for 1 minute at 24 ^° C. The supernatants were then used to determine the decay of ¹²⁵ 1-BH-CCK. Precipitation was washed with ice-cold incubation medium and re-centrifuged for 15 s at 24 ^° C. The tip of the tube was broken off and the radioactivity was measured on a gamma scintillation counter. Nonspecific binding was determined by subtracting specific binding from the total.

In experiments to study the binding time of ¹²⁵ 1-BH-CCK, the incubation was performed in 17x100 mm plastic tubes. The total volume was 4.2 ml, and the final concentration of protein ¹²⁵ 1-BH-CCK and CCK ⁸ was the same as in other experiments. At certain time intervals, 200 ml of the incubation mixture was removed, centrifuged at 10,000 q on a Beckman 152 microcentrifuge, washed and counted as described above. To determine the dissociation of the bound ¹²⁵ 1-BH-CCK, CCK _{8 was} added at a concentration of 1 μΜ to the incubation mixture, which was previously incubated for 60 min with ¹²⁵ 1-BH-CCK. The incubation was continued for another 120 minutes, then aliquots were taken at certain intervals, centrifuged and counted as described above.

P r a d d ¹²⁵ 1-VN-HCC. After incubation with ¹²⁵ 1-BH-CCK, aliquots of 100 ml of medium were added to 0.5 ml of 20% trichloroacetic acid (TCA) along with 0.4 ml of medium containing 5 mg / ml BSA as a carrier protein. After incubation in ice for 30 min, the mixture was centrifuged for 1,000 q for 5 min at 4 ^° C, and the radioactivity of the supernatant and precipitate was measured using a gamma-ray scintillation counter. The decay of ¹²⁵ 1-BH-CCK was calculated as a percentage of the total radioactivity of the medium not precipitated by TCA. First, the label precipitated more than 95% and this value did not change after the label was incubated in a medium without membranes for 3 hours.

Results. The binding of ¹²⁵ 1-BH-CCK to the cerebral cortex particles of mice was initially studied at 24 ^° C and pH 7.4, conditions typically exhibiting specific and saturable binding to the cerebral cortex particles of mice. Under these conditions, specific binding was observed, but was accompanied by the decay of ¹²⁵ 1-BH-CCK tags (Table 2). The addition of bacitracin, an aminopeptidase inhibitor, to the medium reduced label degradation as a function of concentration. In the presence of 0.25 mg / ml bacitracin, CCK binding almost doubled, however, with a further increase in the concentration of bacitracin, binding decreased (Table 2). Therefore, all subsequent studies were performed at a concentration of bacitracin in the medium of 0.25 mg / ml.

Claims (7)

1. Derivatives of N-phenylglycinamide of the general formula I

where R _{1 is} hydrogen, (lower) alkyl;
R ₂ (lower) alkoxy or NR ₅ R ₆ , where R ₅ is (lower) alkoxy, R ₆ phenyl optionally substituted by halogen, or R ₅ and R ₆ together with the nitrogen atom to which they are attached form 3.3- di (lower) alkyl piperidine ring, 3,4-dihydro-2H-benzthiazine-1,4-ring or 1,2,3,4-tetrahydroquinolyl-1-ring;
R _{3 is} quinolyl or phenylamino group in which phenyl is substituted with one or more substituents selected from halogen, lower alkyl, lower alkylthio, carboxyl, monooxy lower alkyl, lower alkoxycarbonyl, hydroxyimino lower alkyl, tetrazolyl-5- (ness.) alkyl, (ness.) alkyl-COOX, -O- (ness.) alkyl-COOX, -CH CH COOH, (ness.) alkyl SO ₃ H;
X is hydrogen, lower alkyl; R ₄ = phenyl substituted with halogen, (ness.) Alkyl, (ness.) Alkoxy, hydroxyl, polyfluoro (ness.) Alkyl, nitro, (ness.) Alkylthio, (ness.) Alkoxycarbonyl, carboxyl, acylamino, methylenedioxy, polyfluoro (ness.) alkoxy, trifluoromethylthio, phenoxy, phenyl, benzyl, phenylamino, di (ness.) alkylamino or CONR _a R _b , where R _a lower alkyl, R _b phenyl, or R _a and R _b together with nitrogen to which they are attached to form a 1,2,3,4-tetrahydroquinolyl-1-yl, 3,3-di (lower) alkyl piperidine, 3,4-dihydro-2H-benzoxazine or morpholine ring. 2. Derivatives of N-phenylglycinamide of the general formula I according to claim 1, characterized in that R _{1 is} hydrogen, R ₂ NR ₅ R ₆ , wherein R ₅ and R ₆ together with the nitrogen atom to which they are attached form 3.3- dimethylpiperidine ring, 1,2,3,4-tetrahydro-1-quinoline ring or 3,4-dihydro-2H-benzothiazine-1,4-ring, R ₃ phenylamino group in which phenyl is substituted with lower alkoxycarbonyl or carboxyl R ₄ is phenyl substituted with a (lower) alkoxy group or CONR _a R _b , where R _{a is} lower alkyl, R _{b is} phenyl. 3. Derivatives of N-phenylglycinamide of the general formula I according to claim 1, characterized in that R _{1 is} hydrogen, R _{2 is a} lower alkoxy group or NR ₅ R ₆ , wherein R _{5 is} lower alkyl, R _{6 is} phenyl optionally substituted with halogen, R _{3 a} phenylamino group whose phenyl ring is substituted with lower alkyl, monooxy (lower) alkyl, carboxyl or a lower alkyl -COOH group, R ₄ phenyl substituted with a halogen, (lower) alkoxy group, hydroxyl, (lower) alkoscarbonyl, or CONR _a R _b, where R _a (lower) alkyl, phenyl R _b, or R _a and R _b together with the nitrogen atom to which they are attached, form 1,2,3,4-tetrahydroquinyl yl-2,3,3-di (lower). alkilpiperidil, 3,4-dihydro-2H-benzoxazine or morpholine. 4. A method of obtaining derivatives of N-phenylglycinamide of General formula I

where R _{1 is} hydrogen or lower alkyl;
R ₂ (ness.) Alkoxy or NR ₅ R ₆ , where R ₅ is (ness.) Alkyl, and R ₆ phenyl, possibly substituted by halogen, or R ₅ and R ₆ together with the nitrogen atom to which they are attached form 3 A 3-dialkylpiperidine ring, a 3,4-dihydro-2H-benzothiazine-1,4-ring or a 1,2,3,4-tetrahydroquinolyl-1-ring;
R _{3 is} quinolyl or phenylamino group in which phenyl is substituted with one or more substituents selected from halogen, lower alkyl, lower alkylthio, carboxyl, monoxy lower alkyl, lower alkoxycarbonyl, lower oxyimino. ) alkyl, tetrazolyl-5- (lower) alkyl, (ness.) alk COOX, -O- (ness.) alk COOX, -CH CH COOX, and (ness.) alk SO ₃ H;
R ₄ phenyl substituted with halogen, lower alkyl, lower alkoxy, hydroxyl, poly (lower) alkyl, nitro, lower alkylthio, lower alkoxycarbonyl, carboxyl, acylamino, methylenedioxy, polyfluoro ( ness.) alkoxy, trifluoromethylthio, phenoxy, phenyl, benzyl, phenylamino, di (ness.) alkylamino or CONR _a R _b , where R _a - (ness.) alkyl and R _b phenyl, or R _a and R _b form together with the nitrogen to which they are attached, the 1,2,3,4-tetrahydroquinolyl-1-st, 3,3-dialkylpiperidine, 3,4-dihydro-2H-benzoxazine or morpholine cycle,
characterized in that the isocyanate of the formula is reacted
OCN R ₉ ,
where R _{9 is a} phenyl radical, optionally substituted with one or more substituents selected from halogen atoms and (lower) alkyl, (lower) alkoxy, (lower) alkylthio, nitro, acyl, cyano, sulfamyl, benzoyl, (ness.) alkoxycarbonyl, (ness.) - alk-O- (ness.) alk, 5-tetrazolyl and tetrazolyl-5- (ness.) alkyl radicals,
with an amino derivative of the formula

where R ₁ , R ₂ and R ₄ have the indicated meanings,
and isolate a product and, if necessary, a compound of formula I, where R ₄ phenyl substituted with lower alkoxy is hydrolyzed to give compound I, where R ₄ phenyl substituted with hydroxyl and / or, if necessary, hydrolyzed compound I containing an ester group to give compound I as the corresponding acid. 5. A method of producing derivatives of N-phenylglycinamide of the general formula I according to claim 1, for which R ₃ is a phenylamino radical, the phenyl ring of which is substituted by at least one radical of the type carboxy-, (lower) alk COOH, -O- (lower) -alkyl COOH, —CH CH COOH and / or R ₄ represents a phenyl radical substituted with a carboxy group, characterized in that the corresponding ester is hydrolyzed. 6. A method of producing derivatives of N-phenylglycinamide of the general formula I according to claim 1, for which R ₄ is a phenyl radical substituted with a hydroxy group, characterized in that the corresponding compound is hydrolyzed, for which R ₄ is a phenyl radical substituted with a lower alkoxy group.  7. A pharmacological composition having an agent for cholecystokinin and gastrin receptors, containing an active principle and pharmacologically acceptable additives, characterized in that it contains an N-phenylglycinamide derivative of the general formula I as claimed in the active principle. 1 3 in a single dose of 10,500 mg. Priority by signs:
03/07/90 when R _{1 is} hydrogen or an alkyl radical, R _{2 is an} alkoxy radical or NR ₅ R ₆ , where R _{5 is an} alkyl radical and R ₆ is a phenyl radical, optionally substituted with a halogen atom, or R ₅ and R ₆ form together with the atom the nitrogen to which they are attached, the cycle of 3,3-dialkylpiperidino, 3,4-dihydro-2H-1,4-benzothiazine or 1,2,3,4-tetrahydro-1-quinolyl, R ₃ quinolyl or phenylamino radical, wherein phenyl is substituted with one or more substituents selected from halogen, alkyl, and R _{4 is a} phenyl radical substituted with halogen, alkyl, alkoxy, nitro, alkylthio, alkoxycarbonyl, acyl foreign, methylenedioxy, trifluoroalkoxy, trifluoromethylthio, phenoxy, phenyl or benzyl;
10.16.90 when R _{1 is} a hydrogen atom or an alkyl radical, R ₂ is an alkoxy radical or NR ₅ R ₆ , where R _{5 is an} alkyl radical and R _{6 is a} phenyl radical, optionally substituted with a halogen atom, or R ₅ and R ₆ form together with the nitrogen atom to which they are attached, the cycle of 3,3-dialkylpiperidino, 3,4-dihydro-2H-1,4-benzothiazine or 1,2,3,4-tetrahydro-1-quinolyl, and either the R ₃ quinolyl radical or phenylamino in which phenyl is substituted by one or more substituents selected from halogen, alkyl, alkylthio, carboxy, monohydroxyalkyl, alkoxycarbonyl, hydroxyiminoalkyl, alk-COOX, -O- lx-COOH, -CH CH COOX and alk-SO ₃ H, R ₄ radical is phenyl, substituted by hydroxy, triftormetilkarboksi, trifluoromethoxy, phenylamino, dialkylamino or CONR _a R _b, where R _a alkyl radical and a phenyl radical R _b or R _a and R _b form together with the nitrogen atom to which they are bonded a 1,2,3,4-tetrahydro-1-quinolyl or 3,3-dialkylpiperidino ring, or R _{3 a} phenylamino radical in which phenyl is substituted with one or more substituents selected include carboxy, monohydroxyalkyl, alkoxycarbonyl, gidroksiiminoalkila, -alk-COOX or O-alk-COOX, -CH CH - COOX and alk-SO ₃ H, R ₄ phenyl radical substituted gal gene, alkyl, alkoxy, hydroxy, trifluoromethoxy, nitro, alkylthio, alkoxycarbonyl, carboxy, acylamino, methylenedioxy, trifluoromethoxy, trifluoromethylthio, phenoxy, phenyl, benzyl, phenylamino, dialkylamino or -CONR _a R _b, where R _a alkyl radical, R _b the phenyl radical or R _a and R _b together form a 1,2,3,4-tetrahydro-1-quinolyl or 3,3-dialkylpiperidino ring;
03/05/91 when R _{1 is} a hydrogen atom or an alkyl radical, R ₂ is an alkoxy radical or NR ₅ R ₆ , where R _{5 is an} alkyl radical and R _{6 is a} phenyl radical, optionally substituted with halogen, or R ₅ and R ₆ form together with the atom the nitrogen to which they are attached, a cycle of 3,3-dialkylpiperidino, 3,4-dihydro-2H-1,4-benzothiazine or 1,2,3,4-tetrahydro-1-quinolyl, or R _{3 of} 5-tetrazolylalkyl radical and R ₄ phenyl radical substituted by halogen, alkyl, alkoxy, hydroxy, trifluoromethoxy, nitro, alkylthio, alkoxycarbonyl, carboxy, acylamino, methylenedioxy, trifluoromethoxy, trifluoromethylthio, phenoxy, f Neal, benzyl, phenylamino, dialkylamino or CONR _a R _b, where R _a alkyl radical and R _b represents a phenyl radical or R _a and R _b form together with the nitrogen atom to which they are bonded, 1,2,3,4-cycle tetrahydro-1-quinolyl, 3,3-dialkylpiperidino, 3,4-dihydro-2Nobenzoxazine or morpholino, or R _{3 is a} quinolyl or phenylamino radical in which phenyl is substituted with one or more substituents selected from halogen, alkyl, alkylthio, carboxy, monohydroxy , alkoxycarbonyl, hydroxyiminoalkyl, 5-tetrazolylalkyl, alk-COOX, -O-alk-COOX, -CH = CH-COOX and alk-SO ₃ H, and R ₄ radical CONR _a R _b , where R _a and R _b form, together with the nitrogen atom to which they are bonded, a 3,4-dihydro-2H-benzoxazine or morpholino ring.

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